Bao_2025_Proc.Natl.Acad.Sci.U.S.A_122_e2417104122

Biodegradable polylactic acid (PLA) plastics have been praised as an effective solution to the global pollution caused by petroleum-based plastics, and their widespread use in food packaging and disposable tableware has resulted in increased oral exposure to PLA microplastics (PLA-MPs). Despite their eco-friendly and biodegradable reputation, the in vivo behaviors of PLA-MPs concerning fermentation, carbon cycle, and adverse effects remain unknown. Here, we showed that gut microbiota from the colon can effectively degrade the PLA-MPs by secreting esterase FrsA, whereas esterase FrsA-producing bacteria were identified to dominate this behavior in male C57BL/6 mice. Using isotope tracing and multiomics techniques, we uncovered that (13)C-labeled PLA-MPs were incorporated into the carbon cycle of gut microbiota as a carbon source. Meanwhile, these degraded PLA-MPs fragments entered the succinate pathway of the tricarboxylic acid cycle within gut epithelial cells. These processes altered the metabolic phenotype of the gut, resulting in the decreased linear short-chain fatty acids that are primary energy sources of the gut epithelium. Furthermore, we found that exposure of PLA-MPs significantly reduced the appetite and body weight of mice. Our findings present an overall process of biodegradable plastics within hosts, with the focus on the entire double carbon cycle of PLA-MPs in the gut, which offers indispensable insights into the potential impact of exposure to PLA-MPs.