Resveratrol ameliorates PM2.5-aggravated IBS-D mouse symptoms by restoring the gut bacteria and hypoxanthine/linoleic acid metabolism homeostasis.

Fine particulate matter (PM2.5) is an emerging environmental risk factor for gut disorders. Still, the toxicity of PM2.5 in diarrhea-predominant irritable bowel syndrome (IBS-D) mice and the intervention role of resveratrol remain unclear. This study integrated non-targeted metabolomics and gut microbiota analysis in mice of IBS-D, PM2.5 exposure, and resveratrol + PM2.5 + IBS-D. The colonic histopathology, oxidative stress, colon barrier function, and visceral hypersensitivity were detected. Results showed that PM2.5 significantly exacerbated IBS-D symptoms in mice. Such effects were accompanied by gut microbiota dysbiosis and distinct alterations in fecal metabolites. This study identified an imbalance in faecal microbiota composition in IBS-D and PM2.5 + IBS-D mice, triggering alterations in hypoxanthine and linoleic acid metabolism pathways. Resveratrol alleviated the aggravated IBS-D symptoms by restoring the metabolic pathways. These findings demonstrate that PM2.5 exacerbates IBS-D by disrupting gut microbiota and specific metabolites related to metabolism pathways, and that resveratrol counteracts these effects.