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Polyphenols, present in a broad range of plants, have been thought to be responsible for many beneficial health effects, such as an antidepressant. Despite that polyphenols can be absorbed in the small intestine directly, most of them have low bioavailability and reach the large intestine without any modifications due to their complex structures. The interaction between microbial communities and polyphenols in the intestine is important for the latter to exert antidepressant effects. Gut microbiota can improve the bioavailability of polyphenols; in turn, polyphenols can maintain the intestinal barrier as well as the community of the gut microbiota in normal status. Furthermore, gut microbita catabolize polyphenols to more active, better-absorbed metabolites, further ameliorating depression through the microbial-gut-brain (MGB) axis. Based on this evidence, the review illustrates the potential role of gut microbiota in the processes of polyphenols or their metabolites acting as antidepressants and further envisions the gut microbiota as therapeutic targets for depression.

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Non-alcoholic fatty liver disease (NAFLD), an emerging global health problem affecting 25–30% of the total population, refers to excessive lipid accumulation in the liver accompanied by insulin resistance (IR) without significant alcohol intake. The increasing prevalence of NAFLD will lead to an increasing number of cirrhosis patients, as well as hepatocellular carcinoma (HCC) requiring liver transplantation, while the current treatments for NAFLD and its advanced diseases are suboptimal. Accordingly, it is necessary to find signaling pathways and targets related to the pathogenesis of NAFLD for the development of novel drugs. A large number of studies and reviews have described the critical roles of bile acids (BAs) and their receptors in the pathogenesis of NAFLD. The gut microbiota (GM), whose composition varies between healthy and NAFLD patients, promotes the transformation of more than 50 secondary bile acids and is involved in the pathophysiology of NAFLD through the GM-BAs axis. Correspondingly, BAs inhibit the overgrowth of GM and maintain a healthy gut through their antibacterial effects. Here we review the biosynthesis, enterohepatic circulation, and major receptors of BAs, as well as the relationship of GM, BAs, and the pathogenesis of NAFLD in different disease progression. This article also reviews several therapeutic approaches for the management and prevention of NAFLD targeting the GM-BAs axis.

Obesity, a well-known risk factor in multiple metabolic diseases, is dramatically increasing worldwide. Ginsenosides extracted from ginseng have been reported against obesity and the associated metabolic disorders. As a subtype of ginsenoside, ginsenoside Ro is a critical constituent of ginseng. However, its specific effects on obesity remains unknown. G protein-coupled bile acid receptor 5 (TGR5, also known as GPBAR1) is a bile acid membrane receptor, widely expressed in human tissues contributing to various metabolic processes to confer the regulations of glucose and lipid homeostasis. TGR5 has displayed potentials as a therapeutic target for the treatment of metabolic disorders. Here, we explore the anti-obesity effect of ginsenoside Ro with TGR5 activation screened by a library of natural products. Our results showed that the ginsenoside Ro (90mg/kg) treatment ameliorated body weight and lipid accumulation in multiple metabolic organs of high fat diet-induced obese (DIO) mice without affecting food intake, and improved oral glucose tolerance tests (OGTT), intraperitoneal insulin tolerance tests (IPITT), and fasting serum glucose. We also found that triglyceride (TG) and total cholesterol (TC) in serum and liver were significantly decreased after ginsenoside Ro treatment. Then we used Tgr5 knockout mice to explore the role of Tgr5 in the anti-obesity effect of ginsenoside Ro. Our results further demonstrated that ginsenoside Ro promoted glucagon-like peptide-1 (GLP-1) secretion and energy expenditure in wild type DIO mice. However, the stimulation of ginsenoside Ro on GLP-1 secretion and energy expenditure were restrained in the Tgr5 knockout mice.In conclusion, our findings demonstrated that ginsenoside Ro ameliorates obesity and insulin resistance in DIO mice via activating TGR5, indicatinga potential therapeutic role of ginsenoside Ro to treat obesity and its associated metabolic diseases. SIGNIFICANCE STATEMENTObesity is dramatically increasing worldwide and it contributes to multiple metabolic diseases.TGR5 is a potential therapeutic target for the treatment of metabolic disorders. Ginsenoside Ro, as a oleanane-type ginsenoside, ameliorates obesity and insulin resistance, promotes GLP-1 secretion, This article has not been copyedited and formatted. The final version may differ from this version.