Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital of Basel, CH-4031 Basel, Switzerland.
Cells. 2019 May 14;8(5):450. doi: 10.3390/cells8050450.
Increasing evidence has indicated that diet and metabolites, including bacteria- and host-derived metabolites, orchestrate host pathophysiology by regulating metabolism, immune system and inflammation. Indeed, autoimmune diseases such as inflammatory bowel disease (IBD) are associated with the modulation of host response to diets. One crucial mechanism by which the microbiota affects the host is signaling through G protein-coupled receptors (GPCRs) termed metabolite-sensing GPCRs. In the gut, both immune and nonimmune cells express GPCRs and their activation generally provide anti-inflammatory signals through regulation of both the immune system functions and the epithelial integrity. Members of GPCR family serve as a link between microbiota, immune system and intestinal epithelium by which all these components crucially participate to maintain the gut homeostasis. Conversely, impaired GPCR signaling is associated with IBD and other diseases, including hepatic steatosis, diabetes, cardiovascular disease, and asthma. In this review, we first outline the signaling, function, expression and the physiological role of several groups of metabolite-sensing GPCRs. We then discuss recent findings on their role in the regulation of the inflammation, their existing endogenous and synthetic ligands and innovative approaches to therapeutically target inflammatory bowel disease.
越来越多的证据表明，饮食和代谢物（包括细菌和宿主来源的代谢物）通过调节代谢、免疫系统和炎症来协调宿主的病理生理学。事实上，像炎症性肠病（IBD）这样的自身免疫性疾病与宿主对饮食的反应的调节有关。微生物群影响宿主的一个关键机制是通过称为代谢物感应 G 蛋白偶联受体（GPCR）的 G 蛋白偶联受体（GPCR）进行信号转导。在肠道中，免疫细胞和非免疫细胞都表达 GPCR，它们的激活通常通过调节免疫系统功能和上皮完整性提供抗炎信号。GPCR 家族成员作为微生物群、免疫系统和肠上皮之间的联系，所有这些成分都至关重要地参与维持肠道内稳态。相反，GPCR 信号转导受损与 IBD 及其他疾病有关，包括肝脂肪变性、糖尿病、心血管疾病和哮喘。在这篇综述中，我们首先概述了几类代谢物感应 GPCR 的信号转导、功能、表达和生理作用。然后，我们讨论了它们在调节炎症中的作用、现有的内源性和合成配体，以及创新性的治疗策略，以靶向治疗炎症性肠病。
