Lactobacillus plantarum and Galacto-Oligosaccharides Synbiotic Relieve Irritable Bowel Syndrome by Reshaping Gut Microbiota and Attenuating Mast Cell Hyperactivation

Background: Irritable bowel syndrome (IBS) significantly impairs the lifestyle and quality of life of the global population. However, the underlying pathophysiological mechanisms remain largely elusive. While conventional pharmacological approaches show limited therapeutic efficacy, emerging microbiota-targeted dietary interventions present promising alternatives. Objectives: The present study aimed to elucidate the molecular mechanisms by which a synbiotic mitigates IBS and associated colonic dysfunctions in C57BL/6 mice. Methods: The mouse model was induced by a Citrobacter rodentium (C. rodentium) infection combined with water avoidance stress (WAS). Galacto-oligosaccharides (GOS) were identified as the optimal carbon source for the growth of Lactobacillus plantarum ZYC501 (L. plantarum ZYC501), leading to the establishment of the synbiotic formulation. Results: The 32-day synbiotic intervention, consisting of L. plantarum ZYC501 (1 &times: 109 CFU/day) and GOS (10 g/L, w/w), significantly alleviated colonic transit dysfunction, visceral hypersensitivity, and anxiety-like behaviors in IBS mice. The synbiotic treatment significantly inhibited the expression levels of histamine, mast cell tryptase, and prostaglandin E2 (PGE2) (p &lt: 0.05). The synbiotic also suppressed colonic inflammation by reducing the levels of lipopolysaccharide (LPS), TNF-&alpha:, and IL-6 (p &lt: 0.05). Moreover, the synbiotic increased the expression of MUC2 and the production of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate (p &lt: 0.05). In terms of gut microbiota modulation, the synbiotic reshaped the gut microbiota composition, increasing the abundance of Lactobacillus and Akkermansia while decreasing the levels of Helicobacter and Saccharibacteria. Correlation analysis further revealed a strong association among SCFAs, colonic inflammation, and the gut microbiota. Conclusions: In conclusion, the synbiotic composed of L. plantarum ZYC501 and GOS effectively alleviates IBS and associated colonic dysfunctions by modulating the gut microbiota, reducing mast cell hyperactivity, and enhancing colonic barrier integrity. These findings provide a theoretical basis for developing gut microbiota-targeted dietary interventions for the management of IBS and improvement in gut health.