Role of gut microbiota and fecal metabolites in the protective effect of soybean pulp-rich diet against estrogen-induced cholestasis in rats

Abstract

This study was designed to explore the role of gut microbiota and its metabolites in the treatment of estrogen-induced cholestasis (EIC) in rats with a soybean pulp-rich diet and to clarify the effects of daidzein (DAI), a principal active ingredient of soybean pulp. The findings demonstrated that the soybean pulp-rich diet could relieve cholestasis by decreasing the levels of total bile acids (TBA) and alkaline phosphatase and enhancing the bile flow rate. Through gut microbiota and metabolomics analyses, it was revealed that this diet might alter the abundances of certain bacterial taxa including Akkermansia, Bacteroides, and Turicibacter, thus influencing lipid metabolism, tryptophan metabolism, and steroid metabolism, which led to disparities between the groups fed with and without the soybean pulp-rich diet. Moreover, the soybean pulp-rich diet could modulate the abundances of Prevotella spp. and Tyzzerella, reducing EIC by regulating lipid metabolism and short-chain fatty acids synthesis. Notably, DAI treatment significantly alleviated the abnormalities in serum TBA, alanine aminotransferase, and aspartate aminotransferase levels and mitigated the liver tissue damage in the EIC model. In summary, during cholestasis, variations in gut microbiota and metabolite profiles occurred. The intervention of soybean pulp affected the abundances of bacteria (such as Prevotella spp. and Tyzzerella) and regulated lipid metabolism-related pathways. Importantly, DAI was identified as a crucial component for the protective effects associated with the soybean pulp diet.