Gut Bacterial Tryptophanase Activity Suprresses Ethanol-Induced Liver Injury
Alcohol consumption leads to disruptions to the gut microbiota including a depletion of tryptophan-derived indole metabolites. Disrupted tryptophan metabolism is clearly associated with alcohol-associated liver disease, yet our understanding of the specific role of gut microbe-driven tryptophan metabolism has been hampered due to lack of mouse models. To address this, we created a defined synthetic microbial community with either intact or genetically deleted tryptophanase activity for in vivo studies. Gnotobiotic mice lacking bacterial tryptophanase activity are more susceptible to ethanol-induced liver injury. Interestingly, mice with intact microbial tryptophanase activity have a robust induction of IL-6 and acute phase proteins when challenged with ethanol. Furthermore, bacterial tryptophanase activity promoted a spatial reorganization of the gut microbiome and colonization of Akkermansia muciniphila within the ileum. Collectively, this study highlights the functional importance of bacterial tryptophan metabolites in shaping ethanol-driven reorganization of the gut microbiome and host immune response to promote liver injury.