G Protein-Coupled Receptors in Irritable Bowel Syndrome: Mechanisms and Therapeutic Opportunities

TL;DR

This review explores how G protein-coupled receptors (GPCRs) contribute to IBS and highlights their potential as therapeutic targets.

Contribution

The paper provides a mechanistic framework for GPCR-based therapies in IBS by integrating recent findings on immune, microbiota, and neural signaling.

Findings

GPCRs mediate signals from microbial metabolites to regulate gut homeostasis in IBS.

External substances like fats and histamine influence immune and neural functions via GPCRs.

Challenges remain in targeting GPCRs due to patient heterogeneity and microbiome complexity.

Abstract

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.

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