Polyethylene Microplastic Exposure Disrupts Sex and Gut Hormones via Gut Microbial and Metabolic Pathways

Microplastics (MPs) disrupt the endocrine system by interfering with hormone production, signaling, and function, which can lead to hormonal imbalances and developmental disorders. This study systematically examined the effects of polyethylene (PE) MPs on circulatory hormone levels, uncovering the underlying mechanisms involving gut microbiota dysbiosis and metabolic changes. Female mice were exposed to PE MPs for 4 weeks, after which plasma levels of sex and enteropancreatic hormones were measured. Gut microbiota composition was analyzed through 16S rDNA sequencing, and plasma metabolites were profiled using high-throughput targeted metabolomics. The results revealed that PE MPs exposure significantly reduced circulating levels of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), Anti-Müllerian hormone (AMH), and testosterone. Moreover, PE MPs notably altered the gut microbial community and plasma metabolite profile, with significant reductions in Akkermansia abundance and its associated metabolites, such as myristic acid and phenylacetylglycine. In vitro studies with primary colonic cells showed that myristic acid increased GLP-1 secretion through the G-protein coupled receptor 120 (GPR120), while phenylacetylglycine enhanced GLP-1 secretion via the peptide transporter 1 (Pept1). Additionally, Akkermansia abundance and its metabolites were strongly positively correlated with plasma levels of PYY, AMH, and testosterone. In conclusion, exposure to PE MPs disrupted hormonal release, likely mediated by alterations in gut microbiota-particularly Akkermansia-and associated metabolites.