Novel myo -inositol to butyrate fermentation pathway in the prevalent human gut species Dysosmobacter welbionis, a bacterium associated with improved metabolic and liver health

Background Dysosmobacter welbionis is a recently discovered butyrate producer whose presence in stool correlates with improved metabolic health. Whether its abundance is reduced in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. Mechanistic insight into its butyrate production from myo -inositol, a dietary compound from fruits, beans, grains and nuts with metabolic benefits, is also limited. Objective To assess population-level distribution, relative abundance and strain diversity of D. welbionis in humans, and to elucidate its metabolic capacity to ferment myo -inositol into butyrate. Design We analysed several human cohorts for associations with liver health and evaluated D. welbionis J115 T supplementation in a diet-induced steatosis mouse model. An antibody-guided anaerobic cell-sorting strategy enabled isolation of distinct strains. We combined 13 C-labelled inositol isotopes with NMR, mass spectrometry, genomics and proteomics. Results We found that D. welbionis and two related species ( D. hominis and D. segnis ) are prevalent gut bacteria in the human gut. D. welbionis abundance was reduced in MASLD across two cohorts and inversely correlated with fibrosis score in a third cohort. Treatment with D. welbionis J115 T improved glycaemia and hepatic steatosis in high-fat diet fed mice. We identified a non-canonical myo -inositol-to-butyrate fermentation pathway. 19 human strains were isolated, comparative genomics of 23 strains revealed an open pangenome (about 2100 core genes) including the full myo- inositol fermentation pathway. Conclusion D. welbionis possesses a unique, conserved route to convert dietary myo -inositol into butyrate, distinguishing it from other commensals and supporting its potential as a next-generation probiotic for metabolic and liver health.