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

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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

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Figure 3

Strategies for MBIs.

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Strategies for MBIs.
The “Untreated” panel schematically depicts a micro...
The “Untreated” panel schematically depicts a microbial community. “Ablation” refers to the eradication of the endogenous microbiome via methods like antibiotic treatment or via more targeted approaches like phage therapy. “Replacement” refers to strategies that introduce exogenous microbes into the gut, such as probiotics, synbiotics, FMT, or live biotherapeutics. “Support” represents strategies that involve changing the resource environment to support microbial growth, such as dietary interventions or prebiotics, which provide fermentable fiber sources that are selectively metabolized by gut microbes.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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