Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Clinical innovation and scientific progress in GLP-1 medicine (Nov 2025)
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Emerging concepts and shifting paradigms for understanding the microbial basis of inflammatory bowel diseases
Megan S. Kennedy, Eugene B. Chang
Megan S. Kennedy, Eugene B. Chang
Published September 2, 2025
Citation Information: J Clin Invest. 2025;135(17):e193969. https://doi.org/10.1172/JCI193969.
View: Text | PDF
Review Series

Emerging concepts and shifting paradigms for understanding the microbial basis of inflammatory bowel diseases

  • Text
  • PDF
Abstract

Inflammatory bowel diseases (IBDs) are complex immune disorders that arise at the intersection of genetic susceptibility, environmental exposures, and dysbiosis of the gut microbiota. Our understanding of the role of the microbiome in IBD has greatly expanded over the past few decades, although efforts to translate this knowledge into precision microbiome-based interventions for the prevention and management of disease have thus far met limited success. Here we survey and synthesize recent primary research in order to propose an updated conceptual framework for the role of the microbiome in IBD. We argue that accounting for gut microbiome context — elements such disease regionality, phase of disease, diet, medication use, and patient lifestyle — is essential for the development of a clear and mechanistic understanding of the microbiome’s contribution to pathogenesis or health. Armed with better mechanistic and contextual understanding, we will be better prepared to translate this knowledge into effective and precise strategies for microbiome restitution.

Authors

Megan S. Kennedy, Eugene B. Chang

×

Figure 1

Contextual drivers of the microbiome in IBD.

Options: View larger image (or click on image) Download as PowerPoint
Contextual drivers of the microbiome in IBD.
The specific role played by...
The specific role played by the microbiome in IBD varies across a wide variety of contextual factors. Sleep and circadian rhythms impact the rhythmicity and functional output of the microbiota. Diet affects composition and function of the microbiota. Medications can affect microbiome composition, and the microbiota can reciprocally impact drug metabolism. Across stages of disease from diagnosis to relapse, microbiota composition varies in ways that may help to predict disease activity. Different IBD subtypes are associated with distinct microbiome signature. Distinct regions of the GI tract harbor distinct microbiota profiles both in health and in disease. Exercise and lifestyle impact the microbiota both directly and via effects on motility of the GI tract. Early-life exposures may alter tolerance to commensal microbes, and even the healthy microbiota varies over the human lifespan.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts