Gut microbiome composition and metabolic activity in women with diverticulitis

Wenjie Ma, Yiqing Wang, Long H. Nguyen, Raaj S. Mehta, Jane Ha, Amrisha Bhosle, Lauren J. Mclver, Mingyang Song, Clary B. Clish, Lisa L. Strate, Curtis Huttenhower and Andrew T. Chan ()
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Wenjie Ma: Massachusetts General Hospital and Harvard Medical School
Yiqing Wang: Massachusetts General Hospital and Harvard Medical School
Long H. Nguyen: Massachusetts General Hospital and Harvard Medical School
Raaj S. Mehta: Massachusetts General Hospital and Harvard Medical School
Jane Ha: Massachusetts General Hospital and Harvard Medical School
Amrisha Bhosle: Harvard T.H. Chan School of Public Health
Lauren J. Mclver: Harvard T.H. Chan School of Public Health
Mingyang Song: Massachusetts General Hospital and Harvard Medical School
Clary B. Clish: Broad Institute of MIT and Harvard
Lisa L. Strate: University of Washington School of Medicine
Curtis Huttenhower: Harvard T.H. Chan School of Public Health
Andrew T. Chan: Massachusetts General Hospital and Harvard Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.

Date: 2024
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DOI: 10.1038/s41467-024-47859-4

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