Infectious Disease and Microbiome Program / en Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections /news/scientists-identify-unique-combination-bacterial-strains-could-treat-antibiotic-resistant-gut <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source 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media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h" alt="Microscope image showing E. coli." title="Microscope image showing E. coli." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health </div> <div class="media-caption__description"> Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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</article> </div> <div class="node__content"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source 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800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=pOrxT6K5 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN" alt="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Wed, 18 Sep 2024 14:51:33 +0000 adicorat 5557391 at Gut microbiome changes align with increased risk of type 2 diabetes /news/gut-microbiome-changes-fuel-increased-risk-type-2-diabetes <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h" alt="Microscope image showing E. coli." title="Microscope image showing E. coli." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health </div> <div class="media-caption__description"> Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=chf1TO-i 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=chf1TO-i 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=8IJyhoav 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=8IJyhoav 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=d3K7IF43 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=YEGLY1jE 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=YEGLY1jE" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=pOrxT6K5 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN" alt="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Tue, 25 Jun 2024 13:30:11 +0000 tulrich@broadinstitute.org 5557066 at Scientists link certain gut bacteria to lower heart disease risk /news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h" alt="Microscope image showing E. coli." title="Microscope image showing E. coli." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health </div> <div class="media-caption__description"> Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons 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class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=chf1TO-i 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=chf1TO-i 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=8IJyhoav 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=8IJyhoav 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=d3K7IF43 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=YEGLY1jE 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=YEGLY1jE" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=pOrxT6K5 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN" alt="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Tue, 02 Apr 2024 15:00:00 +0000 adicorat 5556761 at Researchers uncover genetic factors for severe Lassa fever /news/researchers-uncover-genetic-factors-severe-lassa-fever <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h" alt="Microscope image showing E. coli." title="Microscope image showing E. coli." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health </div> <div class="media-caption__description"> Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons 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class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk"><picture> <source 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=d3K7IF43 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=YEGLY1jE 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/oscillibacter_main.png?h=4693aea5&amp;itok=YEGLY1jE" alt="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." title="Microscope image of Oscillibacter bacteria that have taken up cholesterol, which is labeled with a fluorescent dye." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=pOrxT6K5 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN" alt="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Thu, 08 Feb 2024 14:00:00 +0000 adicorat 5556161 at With AI, researchers identify a new class of antibiotic candidates /news/researchers-use-ai-identify-new-class-antibiotic-candidates <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h" alt="Microscope image showing E. coli." title="Microscope image showing E. coli." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health </div> <div class="media-caption__description"> Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons 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class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk"><picture> <source 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href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=pOrxT6K5 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN" alt="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Wed, 20 Dec 2023 16:30:46 +0000 tulrich@broadinstitute.org 5556221 at Researchers identify gut microbiome signatures linked to precancerous colon polyps /news/researchers-identify-gut-microbiome-signatures-linked-precancerous-colon-polyps <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" 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class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/698/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/698/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" 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field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a 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title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Wed, 14 Jun 2023 12:59:00 +0000 tulrich@broadinstitute.org 1282366 at Viruses in the guts of centenarians may help them resist pathogens /news/viruses-guts-centenarians-may-help-them-resist-pathogens <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source 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href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source 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strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Mon, 15 May 2023 15:00:00 +0000 adicorat 1282201 at How a mother’s microbiome helps shape her baby’s development /news/how-mothers-microbiome-helps-shape-her-babys-development <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source 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href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source 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strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Thu, 22 Dec 2022 16:23:29 +0000 leah@broadinstitute.org 1281401 at ӳý Discovery Center in Cambridge opens to the public this October /news/broad-discovery-center-cambridge-opens-public-october <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source 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href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=pOrxT6K5 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN" alt="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Mon, 19 Sep 2022 14:53:09 +0000 kzusi@broadinstitute.org 1195701 at How the body identifies helpful bacteria /news/how-body-identifies-helpful-bacteria <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" class="datetime">September 18, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The microbes control the growth of harmful bacteria in mice, promoting a healthier intestinal microbiome.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-09-18T10:51:33-04:00" title="Wednesday, September 18, 2024 - 10:51" class="datetime">September 18, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/24661308922_3eb66388f6_o.jpg?itok=bWNpXDEl 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=GsJ8tu4I 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/24661308922_3eb66388f6_o.jpg?itok=0UfvzKMT 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/24661308922_3eb66388f6_o.jpg?itok=SKCuDyLM 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/24661308922_3eb66388f6_o.jpg?itok=jNW3E-4h" alt="Microscope image showing E. coli." title="Microscope image showing E. coli." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health </div> <div class="media-caption__description"> Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons 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class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk"><picture> <source 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href="/news/scientists-link-certain-gut-bacteria-lower-heart-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Scientists link certain gut bacteria to lower heart disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=WlHGJscN 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=Hfhe1K-m 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=pOrxT6K5 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/C.difficile-JaniceCarr-CDC-800X596-1.png?h=d3e04ee7&amp;itok=LOIzNyqN" alt="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." title="Researchers found that a compound made by intestinal microbes in centenarians strongly inhibits the growth of Clostridium difficile (colorized), which causes severe diarrhea and gut inflammation." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/centenarians-have-distinct-microbiome-may-help-support-longevity" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Centenarians have a distinct microbiome that may help support longevity</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as <em>Enterobacteriaceae</em> are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful.&nbsp;</p> <p>Researchers at Keio University School of Medicine in Tokyo and the ӳý of MIT and Harvard have isolated 18 bacterial strains from stool from healthy people that could potentially be a more effective treatment. The team found that these strains suppress the growth of <em>Enterobacteriaceae</em> and alleviate inflammation in the guts of mice by competing with the harmful bacteria for carbohydrates and preventing them from colonizing the intestine.&nbsp;</p> <p>The findings, which appear today in <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank"><em>Nature</em></a>, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.</p> <p>“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” said Marie-Madlen Pust, a computational postdoctoral researcher at ӳý and co-first author on the paper.&nbsp;</p> <p>“Part of the challenge is that each person’s microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she said.</p> <p>“Microbiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial,” said <a href="http://www.broadinstitute.org/node/4721/">Ramnik Xavier</a>, co-senior author on the study and a core institute member at ӳý. “Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation.”</p> <p>Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.</p> <h2>Bacterial balances</h2> <p>Antibiotic-resistant <em>Enterobacteriaceae</em> such as<em> E. coli</em> and <em>Klebsiella</em> bacteria are common in hospitals, where they can proliferate in the gut of patients and cause dangerous systemic infections that are difficult to treat. Some research suggests that <em>Enterobacteriaceae</em> also perpetuates inflammation in the intestine and infection by other microbes. Honda, Xavier, and their colleagues wanted to understand which specific bacteria in fecal microbiota transplants could help protect the intestinal microbiome against <em>Enterobacteriaceae</em>. Honda’s team isolated about 40 strains of bacteria from each stool sample from five healthy donors and used them to treat mice infected with <em>E. coli</em> or <em>Klebsiella</em>. They tested different combinations of strains and identified a group of 18 strains that suppressed the <em>Enterobacteriaceae</em> the most.&nbsp;</p> <p>The Keio University researchers found that in <em>Klebsiella</em>-infected mice treated with the 18 beneficial strains, <em>Klebsiella</em> altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes — indicating increased competition among the gut microbes for nutrients.</p> <p>Xavier’s team wanted to study samples from patients with and without gut inflammation. In partnership with the ӳý’s <a href="/node/8539">Metabolomics Platform</a>, led by senior director and study co-author <a href="/node/7580">Clary Clish</a>, they analyzed samples from pediatric patients with ulcerative colitis, looking for&nbsp; the presence&nbsp; of alternate gluconate pathway genes of gut microbes and fecal gluconate levels. They found higher levels of gluconate linked to more gluconate-consuming Enterobacteriaceae in samples from pediatric patients with ongoing inflammation, indicated by high levels of the protein calprotectin.&nbsp;</p> <p>Together, the findings suggest that <em>Enterobacteriaceae</em> processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with <em>Enterobacteriaceae</em> for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.</p> <p>The 18 strains also did not disrupt the growth of other healthy bacteria in animals with gut microbes from patients with Crohn’s disease and ulcerative colitis, further underscoring their therapeutic promise.&nbsp;</p> <p>Although more work will be needed to shed light on the precise mechanisms underlying how different bacteria compete with each other, the findings suggest that microbial therapeutics could be used to tweak the ecology of the gut and suppress harmful bacterial infections with fewer negative side effects than typical antibiotic treatments.&nbsp;</p> <p>In the meantime, the team aims to uncover the identity and function of unknown metabolites that contribute to gut health and inflammation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Furuichi, M et al. <a href="https://www.nature.com/articles/s41586-024-07960-6" target="_blank">Commensal consortia decolonize <em>Enterobacteriaceae</em> via ecological control</a>. <em>Nature</em>. Online September 18, 2024. DOI:10.1038/s41586-024-07960-6.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/infectious-disease-and-microbiome-0" hreflang="en">Infectious Disease and Microbiome Program</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease-0" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Fri, 16 Sep 2022 15:00:00 +0000 aviveros@broadinstitute.org 1192581 at