Gut Microbiota‐Bile Acid Axis Correlates With Colonic Inflammation and Behavioral Deficits in Cirrhosis

OBJECTIVES: Hepatic encephalopathy (HE) is one of the common complications of cirrhosis. Gut-derived signals, including microbiota and bile acids, have been found to be involved in the gut-brain axis in cirrhosis. We aimed to explore the impact of the gut-microbiota-bile acid axis on behavioral deficits in cirrhosis. METHODS: Mice were colonized with gut bacteria obtained from cirrhotic patients with or without HE via fecal microbiota transplantation. Serum bile acid profiles, intestinal histological features, and behaviors were assessed to evaluate the impacts of gut microbial disturbance on bile acids and gut-brain axis. Additionally, rodent cirrhotic models were induced by bile duct ligation (BDL), and the mice were treated with obeticholic acid (OCA) or rifaximin to evaluate the impact of bile acid remodeling on gut bacteria, gut injury, and behaviors. The 16S rRNA sequencing and LC-MS/MS were carried out to analyze gut microbiota composition and bile acid spectrum. RESULTS: Gut bacteria transplanted from cirrhotic patients caused reduced levels of total and secondary bile acids in mice, which was accompanied by increased colonic lymphocytic infiltration, decreased exploratory behaviors, and higher expression of IBA-1. OCA intervention improved gut dysbiosis, alleviated liver injury and exploratory behavior impairment in the cirrhotic mouse model, accompanied by increased Farnesoid X receptor (FXR) expression and decreased ASBT, IBABP, and OSTα levels. CONCLUSION: Gut microbiota-bile acid axis correlates with colonic inflammation and behavioral deficits in cirrhosis.