The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.

Alcoholic liver disease (ALD) is a major worldwide chronic liver disease accompanied by hepatic inflammation, gut leakiness, and abnormal oxidative stress. Our previous study demonstrated substantial hepatoprotective activity of the active Poria cocos polysaccharide (PCP-1C). The present study explored whether PCP-1C protects against ALD among hepatic inflammation, gut leakiness, and abnormal oxidative stress. The results showed that PCP-1C significantly improved alcohol-induced liver injury by decreasing serum biochemical parameters, alleviating hepatic steatosis, and reducing lipid accumulation caused by ALD. Moreover, PCP-1C treatment reduced hepatic inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and also improved hepatocyte apoptosis by inhibiting the cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/mitogen-activated protein kinases (MAPKs) signaling pathway. Regarding intestinal protection, PCP-1C could repair the intestinal barrier and reduce lipopolysaccharide (LPS) leakage. Generally, PCP-1C exerts a positive therapeutic effect on ALD, which may play a pivotal of decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and improving intestinal barrier injury.

The gut microbiota, shaped by factors such as diet, lifestyle, and genetics, plays a pivotal role in regulating host metabolism, immune function, and overall health. The diversity and balance of the gut microbiota are closely linked to the onset and progression of various chronic diseases. A growing body of evidence has demonstrated that alterations in the composition, function, and metabolites of the gut microbiota are significantly associated with cardiovascular diseases, including hypertension, atherosclerosis, and heart failure; metabolic disorders such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease; and gastrointestinal conditions like inflammatory bowel disease and colorectal cancer. Despite substantial advances in microbiome research, challenges remain in fully elucidating the causal relationships between the gut microbiota and disease, as well as in translating these insights into clinical applications. This review aims to investigate the regulatory pathways via which the gut microbiota affects cardiovascular health, metabolic function, and gastrointestinal disease. Additionally, it highlights emerging strategies for the prevention and treatment of these chronic conditions, focusing on microbiota-targeted therapies and personalized dietary interventions as promising approaches for improving health outcomes.