Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome.

ABSTRACT: Intestinal proteases mediate digestion and immune signalling, while increased gut proteolytic activity disrupts the intestinal barrier and generates visceral hypersensitivity, which is common in irritable bowel syndrome (IBS). However, the mechanisms controlling protease function are unclear. Here we show that members of the gut microbiota suppress intestinal proteolytic activity through production of unconjugated bilirubin. This occurs via microbial β-glucuronidase-mediated conversion of bilirubin conjugates. Metagenomic analysis of faecal samples from patients with post-infection IBS (n = 52) revealed an altered gut microbiota composition, in particular a reduction in Alistipes taxa, and high gut proteolytic activity driven by specific host serine proteases compared with controls. Germ-f

SUBMITTER: Edwinson AL 

PROVIDER: S-EPMC9081267 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature