Theabrownin is one of the most bioactive compounds in Pu-erh tea. Our previous study revealed that the hypocholesterolemic effect of theabrownin was mediated by the modulation of bile salt hydrolase (BSH)-enriched gut microbiota and bile acid metabolism. In this study, we demonstrated that theabrownin ameliorated high-fat-diet (HFD)-induced obesity by modifying gut microbiota, especially those with 7α-dehydroxylation on the species level, and these changed microbes were positively correlated with secondary bile acid (BA) metabolism. Thus, altered intestinal BAs resulted in shifting bile acid biosynthesis from the classic to the alternative pathway. This shift changed the BA pool by increasing non-12α-hydroxylated-BAs (non-12OH-BAs) and decreasing 12α-hydroxylated BAs (12OH-BAs), which improved energy metabolism in white and brown adipose tissue. This study showed that theabrownin was a potential therapeutic modality for obesity and other metabolic disorders via gut microbiota-driven bile acid alternative synthesis.

High-grade serous carcinoma (HGSC) represents a formidable challenge in the realm of ovarian cancer, notorious for its elusive early detection, poor prognosis and limited understanding of the intricacies of its pathogenesis

Hyocholic acid (HCA) and its derivatives are found in only trace amounts in human blood, but constitute approximately 76 % of the bile acid (BA) pool in the pig, a species known for its exceptional resistance to type 2 diabetes mellitus (T2DM). Here we show that HCA species play a crucial role in maintaining glucose homeostasis and preventing T2DM. We found that in two cohort studies (n=1,213), both obesity and diabetes were associated with lower serum concentrations of HCA species. Serum HCA levels in apparently healthy individuals (n=132) were found to be strong predictors for metabolic health 10 years later. Oral administration of HCA increased serum fasting GLP-1, to a greater extent than metformin, in healthy and diabetic mouse models. HCA upregulated GLP-1 secretion in intestinal enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor, a unique mechanism that is not found in other BA species.