Discovery of disease-adapted bacterial lineages in inflammatory bowel diseases
Open accessAbstract
Gut bacteria are implicated in inflammatory bowel disease (IBD), but the strains driving these associations are unknown. Large-scale studies of microbiome evolution could reveal the imprint of disease on gut bacteria, thus pinpointing the strains and genes that may underlie inflammation. Here, we use stool metagenomes of thousands of IBD patients and healthy controls to reconstruct 140,000 strain genotypes, revealing hundreds of lineages enriched in IBD. We demonstrate that these strains are ancient, taxonomically diverse, and ubiquitous in humans. Moreover, disease-associated strains outcompete their healthy counterparts during inflammation, implying long-term adaptation to disease. Strain genetic differences map onto known axes of inflammation, including oxidative stress, nutrient biosynthesis, and immune evasion. Lastly, the loss of health-associated strains of Eggerthella lenta was predictive of fecal calprotectin, a biomarker of disease severity. Our work identifies reservoirs of strain diversity that may impact inflammatory disease and can be extended to other microbiome-associated diseases.
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Kumbhari et al. describe a larger number of associations with a similar IBD sample size (20% of their associations), these associations are generally in small clades, and their top StrainPhlAn association agrees with one of the top associations described in our study, Fusicatenibacter saccharivorans.
“Although Kumbhari et al. describe a larger number of associations with a similar IBD sample size (20% of their associations), these associations are generally in small clades, and their top StrainPhlAn association agrees with one of the top associations described in our study, Fusicatenibacter saccharivorans .”
From Global genetic diversity of human gut microbiome species is related to geographic location and host health (2025) · cites this paper as [30]
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- Kumbhari, A., Cheng, T. N. H., Ananthakrishnan, A. N., Kochar, B., Burke, K. E., Shannon, K., Lau, H., Xavier, R. J., & Smillie, C. S.
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- Smillie, Christopher S.
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- PubMed Central (acceptedVersion)
- Funders
- Crohn's and Colitis Foundation of America (993224)
- Leona M and Harry B Helmsley Charitable Trust
- Croucher Foundation
- National Institutes of Health (R01AI172147, R01DK127171)
- PEW Charitable Trusts
- Crohn's and Colitis Foundation
- Bristol-Myers Squibb
- 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 › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- inflammatory bowel disease, gut microbiota, Eggerthella lenta, fecal calprotectin, oxidative stress, immune evasion, strain diversity
- MeSH terms
- Gastrointestinal Microbiome, Bacteria, Feces, Genotype, Humans, Phylogeny, Inflammatory Bowel Diseases, Metagenome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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