Lactobacillus helveticus R0052 Ameliorates Cholestasis with FXR-Related Pathways and Modulation of Gut Microbiota

Abstract

Cholestasis is an important clinical manifestation of primary sclerosing cholangitis (PSC), leading to liver injury, fibrosis and liver failure. The gut microbiota influences the pathogenesis of cholestatic liver disease by modulating metabolic and immune responses. Our study established a PSC mouse model with a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet and Lactobacillus helveticus R0052 intervention to assess the protective effects of probiotics on the disease. In addition, we investigated the microbiome and transcriptome alterations resulting from L. helveticus R0052 intervention to explore associations between gut microbiota and host metabolism. The results showed that L. helveticus R0052 reduced liver injury and inflammation, and ameliorated cholestasis in DDC-fed mice. These beneficial effects were accompanied by alterations in hepatic FXR-Cyp7a1 and ileal FXR-Fgf15 signaling pathways, modified bile-acid homeostasis, as well as changes in the gut microbiota and their metabolites. Overall, our research findings provide an experimental basis for the potential application of L. helveticus R0052 in the prevention of cholestasis.