Microbiome-Gut-Brain Axis in Irritable Bowel Syndrome: Pathophysiology and Therapeutic Approaches

Abstract

Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder characterized by chronic abdominal pain, bloating, and altered bowel habits, with a substantial impact on quality of life and healthcare systems. In recent years, the gut microbiota has emerged as a central component in its pathophysiology. Patients with IBS exhibit alterations in microbial diversity and composition —known as dysbiosis— that vary according to clinical subtype: diarrhea-predominant, constipation-predominant, or mixed. These alterations are associated with intestinal epithelial barrier dysfunction, low-grade inflammation mediated by mast cells and proinflammatory cytokines, disturbances in fermentation and gas production, and dysregulation of the microbiota-gut-brain axis, a multidirectional communication system integrating the central nervous system, the enteric nervous system, and the gut microbiota. Microbial metabolites —including short-chain fatty acids, serotonin, tryptamine, and histamine— actively participate in the modulation of motility, visceral sensitivity, and neuroimmunoendocrine responses. In this context, microbiota-targeted therapeutic strategies have emerged, including probiotics, prebiotics, synbiotics, a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet, rifaximin, and fecal microbiota transplantation, showing promising but heterogeneous results. Emerging therapies such as postbiotics and phage therapy open new perspectives. This review analyzes the pathophysiological mechanisms linking dysbiosis to IBS and evaluates the main microbiota-directed therapeutic interventions.