Roseburia spp. Abundance Associates with Alcohol Consumption in Humans and Its Administration Ameliorates Alcoholic Fatty Liver in Mice

Although a link between the gut microbiota and alcohol-related liver diseases (ALDs) has previously been suggested, the causative effects of specific taxa and their functions have not been fully investigated to date. Here, we analyze the gut microbiota of 410 fecal samples from 212 Korean twins by using the Alcohol Use Disorders Identification Test (AUDIT) scales to adjust for host genetics. This analysis revealed a strong association between low AUDIT scores and the abundance of the butyrate-producing genus Roseburia. When Roseburia spp. are administered to ALD murine models, both hepatic steatosis and inflammation significantly improve regardless of bacterial viability. Specifically, the flagellin of R. intestinalis, possibly through Toll-like receptor 5 (TLR5) recognition, recovers gut barrier integrity through upregulation of the tight junction protein Occludin and helps to restore the gut microbiota through elevated expression of IL-22 and REG3γ. Our study demonstrates that Roseburia spp. improve the gut ecosystem and prevent leaky gut, leading to ameliorated ALDs. [Display omitted] •The depletion of Roseburia is associated with alcohol consumption in human cohorts•R. intestinalis ameliorates the experimental ALD in mice regardless of viability•Flagellin from R. intestinalis protects on ethanol-disrupted gut barrier functions•The ethanol-induced gut microbiota dysbiosis is restored by R. intestinalis The gut microbiota has been indicated as a critical player in alcoholic liver disease via the gut-liver axis. We identified that Roseburia is strongly negatively associated with high alcohol consumption without significant heritability. The causatively ameliorative effects of Roseburia spp. on experimental ALD were by increasing intestinal tight junctions.