Journal
CELL HOST & MICROBE
Volume 29, Issue 8, Pages 1294-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2021.06.019
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Funding
- National Institutes of Health [RO1 AT009708, P30 DK043351, U19 AI142784, U19 AI110495, R21 DK127227]
- Crohn's and Colitis Foundation Microbiome Initiative
- Crohn's and Colitis Foundation Senior Research Award
- Center for Microbiome Informatics and Therapeutics
- Chleck Family Foundation
- National Medical Research Council
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The intestinal microbiome plays a key role in determining responses to biologic therapy in inflammatory bowel disease. Microbial profiles can help predict clinical therapeutic success and guide the selection of optimal treatments for patients.
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 7 alpha/beta-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.
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