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.