Gut microbiome function predicts response to anti-integrin biologic therapy in Inflammatory Bowel diseases
Open accessAbstract
The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function; 13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment.
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Microbial signatures are being evaluated as a novel class of biomarkers for stratification of efficacy and safety in clinical trials across multiple indications.
“In parallel to microbial therapeutics, microbial signatures are being evaluated as a novel class of biomarkers, applied for stratification of efficacy and safety in clinical trials across multiple indications (Ananthakrishnan et al., 2017; Dubin et al., 2016).”
From Gut microbiome stability and dynamics in healthy donors and patients with non-gastrointestinal cancers (2021) · cites this paper as Ananthakrishnan et al., 2017
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- Authors
- Ananthakrishnan, A. N., Luo, C., Yajnik, V., Khalili, H., Garber, J. J., Stevens, B. W., Cleland, T., & Xavier, R. J.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Xavier, Ramnik J.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 21
- Issue
- 5
- Pages
- 603-610.e3
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC5705050
- OpenAlex
- W2613175376
- Cited by
- 451
- References
- 48
- Citations by year
- 2026: 35 · 2025: 57 · 2024: 54 · 2023: 61 · 2022: 55 · 2021: 62 · 2020: 52 · 2019: 50 · 2018: 20 · 2017: 4
- FWCI
- 14.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK097142, DK43351, DK92405, P30 DK043351)
- Crohn’s and Colitis Foundation
- Helmsley Charitable Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Epidemiology › Microscopic Colitis
- Keywords
- gut microbiota, inflammatory bowel disease, Crohn's disease, ulcerative colitis, vedolizumab, anti-integrin therapy, treatment response prediction, microbial function, Roseburia inulinivorans, Burkholderiales, microbial diversity, clinical remission, neural network classifier
- MeSH terms
- Gastrointestinal Microbiome, Biological Therapy, Butyrates, Colitis, Ulcerative, Crohn Disease, Feces, Humans, Prospective Studies, Inflammatory Bowel Diseases, Integrins, Treatment Outcome, Metagenome, Antibodies, Monoclonal, Humanized
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