Polystyrene microplastics exposure impairs skeletal muscle development by disrupting the gut-muscle axis in Hu sheep

Microplastic pollution is an increasing concern in livestock production. Skeletal muscle development is fundamental to animal growth and meat production, but whether microplastic exposure impairs skeletal muscle in ruminants and whether intestinal injury contributes to this process remain poorly understood. Hu sheep were orally exposed to 50-μm polystyrene microplastics (PS-MPs; 75 mg/animal/day) for 8 weeks. In vivo phenotypic assessments, multi-omics analyses, and an in vitro conditioned-medium transfer model were integrated to evaluate intestinal and skeletal muscle responses. PS-MPs exposure reduced body weight gain and muscle water-holding capacity, disrupted myofiber organization, and was accompanied by jejunal injury and reduced expression of tight-junction-related genes. Multi-omics analyses showed remodeling of the fecal microbiota and metabolic profiles, characterized by decreased fecal indole-related metabolites and reduced taurine- and histidine-related metabolites in skeletal muscle. Skeletal muscle showed decreased p-AKT protein abundance, increased nuclear accumulation of FOXO1, and elevated expression of atrophy-related factors, including FBXO32 and TRIM63. Conditioned medium from PS-MPs-exposed jejunal epithelial cells induced FOXO1 nuclear accumulation and atrophy-related molecular changes in differentiated C2C12 myotubes, whereas taurine partially attenuated these responses. Collectively, these findings link intestinal perturbations to FOXO1-associated skeletal muscle injury following PS-MPs exposure and suggest a contributory role for the gut-muscle axis in Hu sheep.