Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease.

Cell Host Microbe
Authors
Abstract

The intestinal microbiome is a key determinant of responses to biologic therapy in inflammatory bowel disease (IBD). However, diverse therapeutics and variable responses among IBD patients have posed challenges in predicting clinical therapeutic success. In this prospective study, we profiled baseline stool and blood in patients with moderate-to-severe Crohn's disease or ulcerative colitis initiating anti-cytokine therapy (anti-TNF or -IL12/23) or anti-integrin therapy. Patients were assessed at 14 weeks for clinical remission and 52 weeks for clinical and endoscopic remission. Baseline microbial richness indicated preferential responses to anti-cytokine therapy and correlated with the abundance of microbial species capable of 7α/β-dehydroxylation of primary to secondary bile acids. Serum signatures of immune proteins reflecting microbial diversity identified patients more likely to achieve remission with anti-cytokine therapy. Remission-associated multi-omic profiles were unique to each therapeutic class. These profiles may facilitate a priori determination of optimal therapeutics for patients and serve as targets for newer therapies.

Year of Publication
2021
Journal
Cell Host Microbe
Volume
29
Issue
8
Pages
1294-1304.e4
Date Published
2021 Aug 11
ISSN
1934-6069
DOI
10.1016/j.chom.2021.06.019
PubMed ID
34297922
PubMed Central ID
PMC8366279
Links
Grant list
R01 AT009708 / AT / NCCIH NIH HHS / United States
U19 AI110495 / AI / NIAID NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R21 DK127227 / DK / NIDDK NIH HHS / United States
U19 AI142784 / AI / NIAID NIH HHS / United States