Recently, a research team led by Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS) revealed the complete biological fate of PLA-MPs in the gut of mice, particularly focusing on their involvement in the double carbon cycle of gut microbiota and epithelium. Related research entitled “Incorporation of polylactic acid microplastics into the carbon cycle as carbon source to remodel the endogenous metabolism of the gut” was published in Proceedings of the National Academy of Sciences of the United States of America2025.

Microplastic pollution is a severe ecological and environmental issue faced globally and is also one of the important risk factors affecting human health. Against the backdrop that traditional plastic restriction orders find it difficult to break through the dilemma of petroleum-based plastic pollution, polylactic acid (PLA), as a medical biodegradable material approved by the FDA, is increasingly highlighting its strategic value. However, as an important material to replace petroleum-based plastics, although PLA has achieved large-scale application in the field of food packaging, it harbors potential risks: its brittle characteristics make it more likely to generate microplastic particles. These particles can efficiently invade the gut through the food chain and trigger unknown biotransformation processes at the microbiota-host interface, affecting their biological fate. Therefore, precisely deciphering the transformation map of PLA microplastics within the living body is crucial for assessing their safety.

In this study, the research team focused on the in vivo transformation of PLA microplastics (PLA-MPs) in mice. Through spatial functional analysis, they found that the colonic microbiota is the core functional unit for the degradation of PLA-MPs. The specific esterase FrsA secreted by the colonic microbiota can precisely recognize and cleave the ester bonds of PLA through its α/β-hydrolase fold domain, thereby achieving efficient degradation of PLA-MPs. Further integration of the microbiota-protein interaction network with single-strain functional validation confirmed that Helicobacter muridarum and Barnesiella intestinihominis dominate the degradation process of PLA-MPs in the gut, thus providing key targets for targeted regulation of plastic biotransformation.

The research team innovatively combined stable isotope ¹³C labeling with metabolic flux tracing. This approach overcame the challenge of distinguishing signals from endogenous metabolites and exogenous particulate derivatives. For the first time, it was shown that PLA microplastics (PLA-MPs) can enter the double“carbon cycle”of gut microbiota and gut epithelium as a carbon source (Figure 1). This process integrates into the host-microbiota co-metabolic network via two pathways: Microbially, ¹³C-PLA-MPs are metabolized through lactate and aspartate into the purine pathway, driving uric acid synthesis (¹³C-PLA-MPs—¹³C-lactate—¹³C-Aspartate—¹³C-Xanthine—¹³C-Urate). In the gut epithelium, ¹³C-PLA-MPs support the synthesis of amino acids and nucleotide precursors via the succinate hub. Ultimately, PLA-MPs' entry into the gut carbon cycle triggers metabolic reprogramming, reducing short-chain fatty acid production, disrupting energy homeostasis, and reallocating carbon flux. This leads to suppressed host feeding behavior and significant weight loss.

“This work comprehensively maps the dynamic biotransformation pathways of biodegradable microplastics within mice. What’s more, this study is of great significance for assessing the biosafety of degradable plastics and provides important data support for understanding the impact of degradable plastics on human physiological processes”Chen Chunying says, a Professor of NCNST and the senior author of the current work.

Figure. The complete life cycle of PLA-MPs in the gut, including the degradation origin, intermediate carbon cycling process, and terminal biological effects. (Image by CHEN Chunying et al)

Contact:

CHEN Chunying

National Center for Nanoscience and Technology (NCNST)

E-mail: chenchy@nanoctr.cn