Critical roles of G protein-coupled receptors in regulating intestinal homeostasis and inflammatory bowel disease.

G protein-coupled receptors (GPCRs) are a group of membrane proteins that mediate most of the physiological responses to various signaling molecules such as hormones, neurotransmitters, and environmental stimulants. Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the gastrointestinal tract and presents a spectrum of heterogeneous disorders falling under two main clinical subtypes including Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD is multifactorial and is related to a genetically dysregulated mucosal immune response to environmental drivers, mainly microbiotas. Although many drugs, such as 5-aminosalicylic acid, glucocorticoids, immunosuppressants, and biological agents, have been approved for IBD treatment, none can cure IBD permanently. Emerging evidence indicates significant associations between GPCRs and the pathogenesis of IBD. Here, we provide an overview of the essential physiological functions and signaling pathways of GPCRs and their roles in mucosal immunity and IBD regulation.