Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI

Drug‐induced liver injury (DILI) is frequently induced by high dose of acetaminophen (APAP) and is concomitant with disturbances of gut flora. Akkermansia muciniphila is beneficial for the repair of liver injury. Lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide all have anti‐inflammatory and antioxidation effects. The objective of this study is to investigate the potential of lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide (LYC) in improving DILI by increasing the abundance of A. muciniphila. Initially, screening for the optimal concentrations of wolfberry, yam, and chrysanthemum (WYC) or LYC to promote A. muciniphila proliferation in vitro and validated in antibiotic (ATB)‐treated KM mice. Subsequently, APAP‐induced DILI model in BALB/c mice were constructed to examine the treatment effects of LYC. Our findings indicate that the optimal concentration ratio of WYC was 2:3:2, and LYC was 1:1:1. WYC increased A. muciniphila proliferation in vitro and in ATB‐treated mice under this ratio. Meanwhile, LYC increased A. muciniphila abundance in vitro and the combination LYC with A. muciniphila promoted the proliferation of A. muciniphila in ATB‐treated mice. The overdose of APAP resulted in the impairment of the intestinal barrier function and subsequent leakage of lipopolysaccharide (LPS). Moreover, LYC increased A. muciniphila abundance, reduced intestinal inflammation and permeability, and upregulated the expression of the tight junction protein zonula occludens protein 1 (ZO‐1) and occludin contents in the gut. Lastly, LYC inhibited LPS leakage and upregulated hepatic YAP1 expression, ultimately leading to the repair of DILI. The polysaccharides of lycium barbarum, yam, and chrysanthemum (LYC) significantly increased the abundance of Akkermansia muciniphila, reduced inflammation and permeability, and increased tight junction in the gut of mice with drug‐induced liver injury (DILI). Subsequently, the enhanced intestinal barrier function inhibited the leakage of lipopolysaccharide (LPS). The expression level of Yes‐associated protein 1 (YAP1) in liver was upregulated and ultimately ameliorated the liver injury. This study provides a new alternative drug for the treatment of acetaminophen (APAP)‐induced DILI.