Kevin Eggan / en How the gut microbiome may influence ALS outcomes /news/how-gut-microbiome-may-influence-als-outcomes <span class="field field--name-title field--type-string field--label-hidden"><h1>How the gut microbiome may influence ALS outcomes</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2020-05-13T11:04:01-04:00" class="datetime">May 13, 2020</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-layout-builder block-extra-field-blocknodenewsbreadcrumbs"> <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-blocknodenewstitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>How the gut microbiome may influence ALS outcomes</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodenewsbody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><div class="summary-only"> <p> Animal study points to role for the microbiome in why only some individuals carrying a common ALS mutation develop the disease</p> </div> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodenewsextra-field-author-custom"> By Jessica Lau, Harvard Department of Stem Cell and Regenerative Biology </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodenewscreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2020-05-13T11:04:01-04:00" class="datetime">May 13, 2020</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-blocknodenewsfield-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/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=CZkAUWjS 1x" media="all and (min-width: 1921px)" type="image/gif" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=CZkAUWjS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/gif" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=qpzwHlol 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/gif" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=NmGH39ze 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/gif" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=6U6V64NN 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/gif" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=8O8j9m08 1x" media="all and (max-width: 539px)" type="image/gif" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=8O8j9m08" alt="In mice with a common ALS genetic mutation, the spinal cord has high levels of inflammation (red) and immune cells (green)." title="In mice with a common ALS genetic mutation, the spinal cord has high levels of inflammation (red) and immune cells (green)." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kevin S. Smith, Harvard University </div> <div class="media-caption__description"> In mice with a common ALS genetic mutation, the spinal cord has high levels of inflammation (red) and immune cells (green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section content-section_with-sidebars container"> <div class="row"> <div class="content-section__left col-2"> <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/1006/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/1006/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" 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#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1006/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" 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#email" /> </svg> </a> </div> </div> </div> <div class="content-section__main col-8"> <div class="block block-layout-builder block-field-blocknodenewsbody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p> A team of scientists from Harvard University and the ӳý of MIT and Harvard has identified a new gut-brain connection in the neurodegenerative disease amyotrophic lateral sclerosis, or ALS. The researchers found that in mice with a common ALS genetic mutation, changing the gut microbiome using antibiotics or fecal transplants could prevent or improve disease symptoms.</p> <p> Published in the journal <a href="https://www.nature.com/articles/s41586-020-2288-7" target="_blank"><em>Nature</em></a>, the findings provide a potential explanation for why only some individuals carrying the mutation develop ALS. They also point to a possible therapeutic approach based on the microbiome.</p> <p> “Our study focused on the most commonly mutated gene in patients with ALS. We made the remarkable discovery that the same mouse model — with identical genetics — had substantially different health outcomes at our different lab facilities,” said Kevin Eggan, Harvard professor of stem cell and regenerative biology and an institute member at the ӳý. “We traced the different outcomes to distinct gut microbial communities in these mice, and now have an intriguing hypothesis for why some individuals carrying this mutation develop ALS while others do not.”</p> <h2> Different facilities, different outcomes</h2> <p> The researchers initially studied the ALS genetic mutation by developing a mouse model at a Harvard lab facility. The mice had an overactive immune response, including inflammation in the nervous system and the rest of the body, which led to a shortened lifespan.</p> <p> In order to run more detailed experiments, the researchers also developed the mouse model in a lab facility at ӳý, where Eggan is the director of stem cell biology at the <a href="/node/8513/">Stanley Center for Psychiatric Research</a>. Unexpectedly, although the mice had the same genetic mutation, their health outcomes were dramatically different.</p> <p> “Many of the inflammatory characteristics that we observed consistently and repeatedly in our Harvard facility mice weren’t present in the ӳý facility mice. Even more strikingly, the ӳý facility mice survived into old age,” said Aaron Burberry, postdoctoral fellow in the Eggan lab and lead author of the study. “These observations sparked our endeavor to understand what about the two different environments could be contributing to these different outcomes.”</p> <h2> Searching the gut microbiome</h2> <p> Looking for environmental differences between the mice, the researchers homed in on the gut microbiome. By using DNA sequencing to identify gut bacteria, the researchers found specific microbes that were present in the Harvard facility mice but absent in the ӳý facility mice, even though the lab conditions were standardized between facilities.</p> <p> “At this point, we reached out to the broader scientific community, because many different groups have studied the same genetic mouse model and observed different outcomes,” Burberry said. “We collected microbiome samples from different labs and sequenced them. At institutions hundreds of miles apart, very similar gut microbes correlated with the extent of disease in these mice.”</p> <p> The researchers then tested ways to change the microbiome and improve outcomes for the Harvard facility mice. By treating the Harvard facility mice with antibiotics or fecal transplants from the ӳý facility mice, the researchers successfully decreased inflammation.</p> <h2> Gut-brain connection</h2> <p> By investigating the connection between genetic and environmental factors in ALS, the researchers identified an important gut-brain connection. The gut microbiome could influence the severity of disease — whether individuals with the genetic mutation develop ALS, the releated condition frontotemporal dementia, or no symptoms at all&nbsp;— and could be a potential target for therapy.</p> <p> “Our study provides new insights into the mechanisms underlying ALS, including how the most common ALS genetic mutation contributes to neural inflammation,” Eggan said. “The gut-brain axis has been implicated in a range of neurological conditions, including Parkinson’s disease and Alzheimer’s disease. Our results add weight to the importance of this connection.”</p> <p> <em>This study was supported by the Merkin Fund at ӳý, Target ALS, the National Institutes of Health, UCB, and the Harvard Stem Cell Institute.</em></p> <p> <em>Adapted from <a href="https://hscrb.harvard.edu/news/gut-microbiome-influences-als-outcomes/" target="_blank">a press release issued by the Harvard Department of Stem Cell and Regenerative Biology</a>.</em></p> </div> </div> <div class="block block-layout-builder block-field-blocknodenewsfield-news-pappers"> <h2>Paper(s) cited</h2> <div class="clearfix text-formatted field field--name-field-news-pappers field--type-text-long field--label-hidden field__item"><p> Burberry A, et al. <a href="http://www.nature.com/articles/s41586-020-2288-7" target="_blank">C9orf72 suppresses systemic and neural inflammation induced by gut bacteria</a>. <em>Nature</em>. Online May 13, 2020. DOI: 10.1038/s41586-020-2288-7.</p> </div> </div> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodenewsfield-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/kevin-eggan" hreflang="en">Kevin Eggan</a></div> </div> </div> </div> </div> <div class="content-section__right col-2"> <div class="block block-ctools block-entity-viewnode"> <article about="/news/how-gut-microbiome-may-influence-als-outcomes" class="node node--type-news node--promoted node--view-mode-sidebar"> <div class="node__content"> </div> </article> </div> </div> </div> </div> Wed, 13 May 2020 15:04:01 +0000 tulrich@broadinstitute.org 628866 at Research Roundup: May 25, 2018 /news/research-roundup-may-25-2018 <span class="field field--name-title field--type-string field--label-hidden"><h1>How the gut microbiome may influence ALS outcomes</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2020-05-13T11:04:01-04:00" class="datetime">May 13, 2020</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-layout-builder block-extra-field-blocknodenewsbreadcrumbs"> <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-blocknodenewstitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>How the gut microbiome may influence ALS outcomes</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodenewsbody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><div class="summary-only"> <p> Animal study points to role for the microbiome in why only some individuals carrying a common ALS mutation develop the disease</p> </div> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodenewsextra-field-author-custom"> By Jessica Lau, Harvard Department of Stem Cell and Regenerative Biology </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodenewscreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2020-05-13T11:04:01-04:00" class="datetime">May 13, 2020</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-blocknodenewsfield-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/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=CZkAUWjS 1x" media="all and (min-width: 1921px)" type="image/gif" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=CZkAUWjS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/gif" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=qpzwHlol 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/gif" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=NmGH39ze 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/gif" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=6U6V64NN 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/gif" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=8O8j9m08 1x" media="all and (max-width: 539px)" type="image/gif" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2020/Eggan_story_page.gif?h=9423a5c0&amp;itok=8O8j9m08" alt="In mice with a common ALS genetic mutation, the spinal cord has high levels of inflammation (red) and immune cells (green)." title="In mice with a common ALS genetic mutation, the spinal cord has high levels of inflammation (red) and immune cells (green)." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kevin S. Smith, Harvard University </div> <div class="media-caption__description"> In mice with a common ALS genetic mutation, the spinal cord has high levels of inflammation (red) and immune cells (green). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section content-section_with-sidebars container"> <div class="row"> <div class="content-section__left col-2"> <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/1006/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/1006/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" 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#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1006/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" 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#email" /> </svg> </a> </div> </div> </div> <div class="content-section__main col-8"> <div class="block block-layout-builder block-field-blocknodenewsbody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p> A team of scientists from Harvard University and the ӳý of MIT and Harvard has identified a new gut-brain connection in the neurodegenerative disease amyotrophic lateral sclerosis, or ALS. The researchers found that in mice with a common ALS genetic mutation, changing the gut microbiome using antibiotics or fecal transplants could prevent or improve disease symptoms.</p> <p> Published in the journal <a href="https://www.nature.com/articles/s41586-020-2288-7" target="_blank"><em>Nature</em></a>, the findings provide a potential explanation for why only some individuals carrying the mutation develop ALS. They also point to a possible therapeutic approach based on the microbiome.</p> <p> “Our study focused on the most commonly mutated gene in patients with ALS. We made the remarkable discovery that the same mouse model — with identical genetics — had substantially different health outcomes at our different lab facilities,” said Kevin Eggan, Harvard professor of stem cell and regenerative biology and an institute member at the ӳý. “We traced the different outcomes to distinct gut microbial communities in these mice, and now have an intriguing hypothesis for why some individuals carrying this mutation develop ALS while others do not.”</p> <h2> Different facilities, different outcomes</h2> <p> The researchers initially studied the ALS genetic mutation by developing a mouse model at a Harvard lab facility. The mice had an overactive immune response, including inflammation in the nervous system and the rest of the body, which led to a shortened lifespan.</p> <p> In order to run more detailed experiments, the researchers also developed the mouse model in a lab facility at ӳý, where Eggan is the director of stem cell biology at the <a href="/node/8513/">Stanley Center for Psychiatric Research</a>. Unexpectedly, although the mice had the same genetic mutation, their health outcomes were dramatically different.</p> <p> “Many of the inflammatory characteristics that we observed consistently and repeatedly in our Harvard facility mice weren’t present in the ӳý facility mice. Even more strikingly, the ӳý facility mice survived into old age,” said Aaron Burberry, postdoctoral fellow in the Eggan lab and lead author of the study. “These observations sparked our endeavor to understand what about the two different environments could be contributing to these different outcomes.”</p> <h2> Searching the gut microbiome</h2> <p> Looking for environmental differences between the mice, the researchers homed in on the gut microbiome. By using DNA sequencing to identify gut bacteria, the researchers found specific microbes that were present in the Harvard facility mice but absent in the ӳý facility mice, even though the lab conditions were standardized between facilities.</p> <p> “At this point, we reached out to the broader scientific community, because many different groups have studied the same genetic mouse model and observed different outcomes,” Burberry said. “We collected microbiome samples from different labs and sequenced them. At institutions hundreds of miles apart, very similar gut microbes correlated with the extent of disease in these mice.”</p> <p> The researchers then tested ways to change the microbiome and improve outcomes for the Harvard facility mice. By treating the Harvard facility mice with antibiotics or fecal transplants from the ӳý facility mice, the researchers successfully decreased inflammation.</p> <h2> Gut-brain connection</h2> <p> By investigating the connection between genetic and environmental factors in ALS, the researchers identified an important gut-brain connection. The gut microbiome could influence the severity of disease — whether individuals with the genetic mutation develop ALS, the releated condition frontotemporal dementia, or no symptoms at all&nbsp;— and could be a potential target for therapy.</p> <p> “Our study provides new insights into the mechanisms underlying ALS, including how the most common ALS genetic mutation contributes to neural inflammation,” Eggan said. “The gut-brain axis has been implicated in a range of neurological conditions, including Parkinson’s disease and Alzheimer’s disease. Our results add weight to the importance of this connection.”</p> <p> <em>This study was supported by the Merkin Fund at ӳý, Target ALS, the National Institutes of Health, UCB, and the Harvard Stem Cell Institute.</em></p> <p> <em>Adapted from <a href="https://hscrb.harvard.edu/news/gut-microbiome-influences-als-outcomes/" target="_blank">a press release issued by the Harvard Department of Stem Cell and Regenerative Biology</a>.</em></p> </div> </div> <div class="block block-layout-builder block-field-blocknodenewsfield-news-pappers"> <h2>Paper(s) cited</h2> <div class="clearfix text-formatted field field--name-field-news-pappers field--type-text-long field--label-hidden field__item"><p> Burberry A, et al. <a href="http://www.nature.com/articles/s41586-020-2288-7" target="_blank">C9orf72 suppresses systemic and neural inflammation induced by gut bacteria</a>. <em>Nature</em>. Online May 13, 2020. DOI: 10.1038/s41586-020-2288-7.</p> </div> </div> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodenewsfield-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/kevin-eggan" hreflang="en">Kevin Eggan</a></div> </div> </div> </div> </div> <div class="content-section__right col-2"> <div class="block block-ctools block-entity-viewnode"> <article about="/news/how-gut-microbiome-may-influence-als-outcomes" class="node node--type-news node--promoted node--view-mode-sidebar"> <div class="node__content"> </div> </article> </div> </div> </div> </div> Fri, 25 May 2018 16:05:00 +0000 tulrich@broadinstitute.org 275321 at