Effects of imbalanced gut microbial on mice with type a hepatic encephalopathy through the gut-liver-brain axis.

BACKGROUND AND AIMS: The relationship between type A hepatic encephalopathy, a highly lethal disease, and gut microbiota remains unclear, and research on this topic is limited. The objective of our study was to investigate the correlation between an imbalance in the gut microbiota and type A hepatic encephalopathy and the impact of fecal microbiota transplantation.

METHODS

We established a mouse model of gut microbiota disorder and type A hepatic encephalopathy. Feces from grades III and IV type A hepatic encephalopathy mice were transplanted into healthy mice. Antibiotic administration, intestinal symbiosis, and pathogenicity experiments were conducted. Behavioral, biochemical, pathological, 16 S rRNA gene amplicon sequencing analyses, and correlation analyses were performed.

RESULTS

Antibiotic treatment caused a gut microbiota imbalance in mice. The degree of thioacetamide-induced type A hepatic encephalopathy was significantly aggravated after oral antibiotic administration, leading to a decline in the survival curve, accompanied by behavioral, biochemical, and pathological changes, as well as decreased Rikenellaceae levels. Transplanting feces from type A hepatic encephalopathy mice into healthy mice resulted in thioacetamide-like behavioral, biochemical, and tissue changes, as well as a significant decline in the abundance of the gut microbiota, an increase in the abundance of Prevotellaceae NK3B31, and a decrease in the abundance of Akkermansia muciniphila and Odoribacter. Additionally, significant correlations were observed between the abundances of the four intestinal microbial species and the majority of measured indicators in mice with type A hepatic encephalopathy. Notably, Akkermansia muciniphila exhibited particularly strong associations with these indicators. Although significant between-group differences were observed for Bacillus, Paenibacillus, Candidatus Saccharimonas, Escherichia-Shigella, UCG_002, Acinetobacter, and Proteus, no significant correlations were detected between these microbial taxa and any of the measured indicators.

CONCLUSIONS

Gut microbiota disorder aggravates lesions in thioacetamide-induced type A hepatic encephalopathy mice. Transplanting feces from mice with type A hepatic encephalopathy causes healthy mice to exhibit type A hepatic encephalopathy symptoms.