The gastrointestinal tract constantly communicates with the environment, receiving and processing a wide range of information. The contents of the gastrointestinal tract and the gastrointestinal tract generate mechanical and chemical signals, which are essential for regulating digestive function and feeding behavior. There are many receptors here that sense intestinal contents, including nutrients, microbes, hormones, and small molecule compounds. In signal transduction, ion channels are indispensable as an essential component that can generate intracellular ionic changes or electrical signals. Ion channels generate electrical activity in numerous neurons and, more importantly, alter the action of non-neurons simply and effectively, and also affect satiety, molecular secretion, intestinal secretion, and motility through mechanisms of peripheral sensation, signaling, and altered cellular function. In this review, we focus on the identity of ion channels in chemosensing and mechanosensing in the gastrointestinal tract.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, altered motility, and visceral hypersensitivity. Emerging evidence implicates G protein-coupled receptors (GPCRs) as key integrators of microbial, immune, endocrine, and neural signals in IBS pathophysiology. This review summarizes recent advances in understanding how GPCRs mediate gut immune regulation, microbiota–host crosstalk, metabolic signaling, and pain processing in IBS. Recent studies show that microbial metabolites (e.g., short-chain fatty acids, biogenic amines, and lipid mediators) signal through GPCRs on immune cells, epithelia, and neurons to influence intestinal homeostasis. On immune cells and neurons, GPCRs also mediate signals from external substances (such as fats, sugars, histamine, etc.) to regulate immune and neural functions. And there are challenges and future directions in targeting GPCRs for IBS, including patient heterogeneity and the complexity of host–microbiome interactions. This review provides a mechanistic framework for GPCR-based therapies in IBS.