Reshaping of bacterial molecular hydrogen metabolism contributes to the outgrowth of commensalduring gut inflammation.

Abstract

During intestinal inflammation, gut microbial community composition shifts, with notable expansion of Enterobacteriaceae. This study examined published metagenomic datasets from both murine colitis models and inflammatory bowel disease patients, focusing on hydrogen metabolism genes. Bacterial genomes recovered from inflamed gut environments harbored a greater abundance of genes encoding hydrogen-utilizing hydrogenases compared to non-inflamed conditions. Functional validation using a representative Enterobacteriaceae species demonstrated that strains lacking hydrogenase-1 and hydrogenase-2 showed reduced colonization fitness in the inflamed cecum and colon. The utilization of molecular hydrogen was found to depend partly on respiration using inflammation-derived electron acceptors. These findings indicate that hydrogenase activity contributes to microbiota compositional shifts observed in non-infectious colitis.

Mechanism

Hydrogenase-1 and hydrogenase-2 enable Enterobacteriaceae to oxidize molecular hydrogen, coupling this process to respiration using inflammation-derived electron acceptors, thereby enhancing colonization fitness in the inflamed gut.