Investigation of therapeutic effects of rhubarb decoction retention enema on minimal hepatic encephalopathy in rats based on 16S rDNA gene sequencing and bile acid metabolomics

Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE), with high incidence and a high rate of clinically missed diagnosis. Early diagnosis of MHE and effective clinical intervention are of great importance. Rhubarb decoction (RD)-induced retention enema can effectively improve the cognitive function of patients with MHE, whereas disturbances in the enterohepatic circulation of bile acid (BAs) can induce MHE. However, the molecular mechanisms underlying the therapeutic effects of RD have not been examined from the perspective of intestinal microbiota and bile metabolomics. In this study, we investigated the effects of RD-induced retention enema on intestinal microbiota and bile metabolites in rats with CCl4- and TAA-induced MHE. RD-induced retention enema significantly improved liver function, reduced blood ammonia levels, alleviated cerebral oedema and restored cognitive function in rats with MHE. In addition, it increased the abundance of intestinal microbes; partially reversed the disorder in the composition of intestinal microbiota, including the Bifidobacterium and Bacteroides genera; and regulated BA metabolism, such as taurine combined with increased BA synthesis. In conclusion, this study highlights the potential importance of BA enterohepatic circulation for RD to improve cognitive function in MHE rats, providing a new perspective on the mechanism of this herb. The findings of this study will facilitate experimental research on RD and help to develop RD-based strategies for clinical application. •The number of beneficial bacteria decreased and the number of harmful bacteria increased in MHE rats.•The increase of unbound bile acids in bile can increase blood-brain barrier permeability.•Bile acid enterohepatic circulation is crucial in the occurrence and development of MHE.•Rhubarb decoction retention enema can improve the structure of intestinal flora and regulate bile acid metabolism.