Uncovering the Hidden Risks: How PLA and PLGA Microplastics Disrupt Gut Microbiota and Metabolic Health

-glycolic acid) (PLGA) have been widely adopted across various industries. While the toxicity of PLA microplastics has been studied extensively, the biological effects of PLGA microplastics remain largely unknown. Through metagenomic sequencing and untargeted metabolomic profiling, we evaluated the impacts of both PLA and PLGA microplastics on gut bacteria, fungi, virulence factors, microbial metabolic pathways, and metabolites in feces, serum, and liver tissue in this study. Our results demonstrate that both types of biodegradable microplastics disrupt gut microbiota and host metabolic homeostasis. PLA exposure provoked more pronounced changes in gut bacteria, fungi, virulence factors, and fecal and hepatic metabolites. In contrast, microbial metabolic pathways and serum metabolites were more strongly affected by PLGA. Several altered features were common to both microplastics, including enrichment of hepatic metabolic pathways related to valine, leucine, and isoleucine biosynthesis; one-carbon pool by folate; glycine, serine, and threonine metabolism; pantothenate and CoA biosynthesis; taurine and hypotaurine metabolism; and cysteine and methionine metabolism. Other disturbances were material-specific, such as UMP biosynthesis pathways, which were altered exclusively by PLA, while palmitate biosynthesis and unsaturated fatty acid biosynthesis were affected only by PLGA. These findings advance our understanding of the distinct and shared health risks posed by different biodegradable microplastics, providing a clearer basis for assessing their long-term safety.