Polystyrene Microplastics Exacerbate Polycystic Ovary Syndrome via Gut Microbiota-Dependent Depletion of Vitamin B6 in Mice

Microplastics (MPs) have become a widespread environmental contaminant, but their impact on female reproductive health remains poorly understood. Here, we demonstrate that polystyrene microplastics (PS-MPs) exacerbate polycystic ovary syndrome (PCOS) by altering the gut microbiota, leading to vitamin B6 depletion and activation of inflammatory pathways in the ovary. In a DHEA-induced PCOS mouse model, oral exposure to PS-MPs disturbed the intestinal microbial community, marked by reduced Firmicutes and elevated Bacteroidetes, and caused a pronounced decline in both intestinal and systemic vitamin B6 levels. The abundance of Flavonifractor plautii, a key vitamin B6–producing bacterium, declined markedly, correlating with increased ovarian TNF-α and IL-6 expression and activation of the MAPK and NF-κB pathways. These molecular changes were accompanied by oxidative stress, disrupted estrous cyclicity, and abnormal hormone profiles. Notably, oral vitamin B6 supplementation reversed many of these alterations, restoring microbial balance, antioxidant capacity, and ovarian function. Together, these findings identify a gut–vitamin B6–ovary axis that mediates the reproductive toxicity of microplastics. This study reveals a previously unrecognized nutritional mechanism linking environmental exposure to endocrine disruption and suggests that maintaining micronutrient homeostasis may help mitigate microplastic-associated reproductive risks.