Tyagi Anuradha, Kumar Vinay
Department of cBRN, Institute of Nuclear Medicine & Allied Sciences, Delhi, 110054, India.
Department of Medicine, Pennsylvania State University Hershey Medical Centre, Hershey, PA, 17033, USA.
World J Microbiol Biotechnol. 2025 Jun 25;41(7):215. doi: 10.1007/s11274-025-04395-7.
The gut microbiota and bile acid metabolism are intricately linked, playing a crucial role in immune regulation, metabolic processes, and overall health. The gut microbiome, consisting of diverse bacterial genera such as Bacteroides, Clostridium, Lactobacillus, Bifidobacterium, and Eubacterium, facilitates the conversion of primary bile acids into secondary bile acids through enzymatic modifications. Bile acids, synthesized in the liver and modified by gut microbiota, act as signaling molecules that regulate immune responses via bile acid receptors, including the farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (GPBAR1), pregnane X receptor (PXR), vitamin D receptor (VDR), and sphingosine-1-phosphate receptor 2 (S1PR2). Dysbiosis-an imbalance in gut microbial composition-disrupts bile acid metabolism, leading to impaired activation of bile acid receptors and contributing to various diseases. These include inflammatory bowel disease, metabolic disorders such as obesity and type 2 diabetes, autoimmune diseases like multiple sclerosis, and liver conditions such as cholestasis and non-alcoholic fatty liver disease. Dysfunctional bile acid receptor signaling further promotes chronic inflammation, metabolic dysregulation, and disturbances in gut-liver-immune homeostasis. Emerging therapeutic strategies targeting bile acid receptors, restoring microbiota balance, and implementing dietary interventions offer promising avenues for disease prevention and management. This review explores the pivotal role of gut microbiota in modulating immune responses through bile acid receptors and highlights their therapeutic potential in improving treatment outcomes.
肠道微生物群与胆汁酸代谢紧密相连,在免疫调节、代谢过程及整体健康中发挥着关键作用。肠道微生物组由多种细菌属组成,如拟杆菌属、梭菌属、乳杆菌属、双歧杆菌属和真杆菌属,通过酶促修饰促进初级胆汁酸转化为次级胆汁酸。在肝脏中合成并经肠道微生物群修饰的胆汁酸,作为信号分子,通过胆汁酸受体调节免疫反应,这些受体包括法尼醇X受体(FXR)、G蛋白偶联胆汁酸受体1(GPBAR1)、孕烷X受体(PXR)、维生素D受体(VDR)和鞘氨醇-1-磷酸受体2(S1PR2)。生态失调——肠道微生物组成失衡——会破坏胆汁酸代谢,导致胆汁酸受体激活受损,并引发各种疾病。这些疾病包括炎症性肠病、肥胖症和2型糖尿病等代谢紊乱、多发性硬化症等自身免疫性疾病以及胆汁淤积和非酒精性脂肪肝病等肝脏疾病。功能失调的胆汁酸受体信号进一步促进慢性炎症、代谢失调以及肠道-肝脏-免疫稳态的紊乱。针对胆汁酸受体、恢复微生物群平衡以及实施饮食干预的新兴治疗策略为疾病预防和管理提供了有前景的途径。本综述探讨了肠道微生物群通过胆汁酸受体调节免疫反应的关键作用,并强调了它们在改善治疗效果方面的治疗潜力。