Resistant Starch and Microbiota-Derived Secondary Metabolites: A Focus on Postbiotic Pathways in Gut Health and...

Resistant starch (RS) is emerging as a multifunctional dietary component and delivery platform for microbiota-accessible carbohydrates. Upon fermentation by gut microbiota, particularly in the colon, RS generates a wide spectrum of postbiotic compounds-including short-chain fatty acids (SCFAs), indoles, bile acid derivatives, and neuroactive amines such as GABA and serotonin precursors. These metabolites modulate gut-brain signaling, immune responses, and intestinal barrier integrity, which are critical pathways in the pathophysiology of irritable bowel syndrome (IBS). This review synthesizes current knowledge on RS structure, classification, and fermentation dynamics, with a special focus on RS3 due to its practical dietary relevance and strong microbiota-modulatory effects. We highlight emerging evidence from clinical studies supporting RS-mediated improvements in IBS symptoms, microbial diversity, and inflammation. Importantly, RS acts as a smart colonic delivery system by escaping enzymatic digestion in the small intestine and reaching the colon intact, where it serves as a targeted substrate for microbial fermentation into bioactive metabolites. This host-microbiota interplay underpins the development of personalized, microbiome-informed nutrition interventions tailored to specific IBS subtypes. Future directions include omics-based stratification, optimized RS formulations, and predictive algorithms for individualized responses. This review aims to clarify the mechanistic links between RS fermentation and postbiotic production, highlighting its therapeutic potential in IBS management.