Intermittent fasting exacerbates microplastic-induced gut inflammation via Rikenella-mediated regulation of purine metabolism and Th17/Treg balance

The pervasive accumulation of microplastics (MPs) in ecosystems and human bodies has prompted growing concern regarding their biological effects. However, whether intermittent fasting (IF) modulates MP-induced gut injury remains unclear. We established a murine model of chronic oral exposure to 1 μm polystyrene MPs combined with a daily 8-h feeding window. Multi-omics analyses, including 16S rRNA sequencing, untargeted metabolomics, and immune profiling, were performed. In a murine model of chronic oral exposure to 1 μm polystyrene microplastics, IF aggravated colonic inflammation and oxidative stress. 16S rRNA sequencing showed that IF further altered the microplastic-associated gut microbiota, notably reducing Rikenella abundance. Untargeted metabolomics revealed disrupted purine metabolism, including decreased hypoxanthine levels, which positively correlated with Rikenella. Combined MP and IF exposure was associated with an increased Th17/Treg ratio. Supplementation with Rikenella or hypoxanthine partially attenuated inflammatory changes. These findings unveil a previously unappreciated risk of IF under conditions of environmental microplastic exposure, and highlight the necessity of integrating environmental toxicants into evaluations of dietary interventions.