A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules.

ABSTRACT: Changes in the gut microbiome have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a multi-cohort analysis of small molecule biosynthetic gene clusters (BGCs) in 5,306 metagenomic samples of the gut microbiome from 2,033 Inflammatory Bowel Disease (IBD) patients and 833 matched healthy subjects and identified a group of Clostridia-derived BGCs that are significantly associated with IBD. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the IBD-enriched BGCs. Using two mouse models of colitis, we show that the discovered small molecules disrupt gut permeability and exacerbate inflammation in chemically and genetically susce

SUBMITTER: Elmassry MM 

PROVIDER: S-EPMC10871352 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature