Discovery of disease-adapted bacterial lineages in inflammatory bowel diseases

Adarsh Kumbhari; Thomas N H Cheng; Ashwin N Ananthakrishnan; Bharati Kochar; Kristin E Burke; Kevin Shannon; Helena Lau; Ramnik J Xavier; Christopher S Smillie

doi:10.1016/j.chom.2024.05.022

Discovery of disease-adapted bacterial lineages in inflammatory bowel diseases

Cell Host Microbe. 2024 Jul 10;32(7):1147-1162.e12. doi: 10.1016/j.chom.2024.05.022. Epub 2024 Jun 24.

Authors

Adarsh Kumbhari¹, Thomas N H Cheng¹, Ashwin N Ananthakrishnan², Bharati Kochar², Kristin E Burke³, Kevin Shannon⁴, Helena Lau⁵, Ramnik J Xavier⁶, Christopher S Smillie⁷

Affiliations

¹ Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA.
² Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA.
⁴ Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
⁵ Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
⁷ Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA. Electronic address: csmillie@mgh.harvard.edu.

PMID: 38917808
PMCID: PMC11239293 (available on 2025-07-10)
DOI: 10.1016/j.chom.2024.05.022

Abstract

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.

Keywords: IBD; bacterial strains; evolution; inflammation; inflammatory bowel diseases; microbiome; microbiota.

MeSH terms

Bacteria / classification
Bacteria / genetics
Bacteria / isolation & purification
Feces* / microbiology
Gastrointestinal Microbiome*
Genotype
Humans
Inflammatory Bowel Diseases* / microbiology
Metagenome
Phylogeny

Abstract

MeSH terms

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