Microplastic pollution is a severe ecological and environmental issue faced globally and is also one of the important risk factors affecting human health. Polylactic acid (PLA), as a medical biodegradable material approved by the FDA, is an important material to replace petroleum-based plastics, 

Although PLA has achieved large-scale application in food packaging, 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. Therefore, elucidating precisely the transformation map of PLA microplastics within the living body is crucial for assessing their safety.

In a study published in PNAS, a research team led by Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences revealed the complete biological fate of PLA microplastics (PLA-MPs) in the gut of mice, particularly focusing on their microbial fermentation into endogenous metabolites and their involvement in the carbon cycle.

Researchers focused on the in vivo transformation of PLA-MPs. 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 could precisely recognize and cleave the ester bonds of PLA through its α/β-hydrolase fold domain, thereby achieving efficient degradation of PLA-MPs. 

Besides, researchers found that 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, providing key targets for the targeted regulation of plastic biotransformation.

Moreover, researchers 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-MPs can enter the double "carbon cycle" of gut microbiota and gut epithelium as a carbon source. 

This process integrated 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. In the gut epithelium, ¹³C-PLA-MPs support the synthesis of amino acids and nucleotide precursors via the succinate hub. Ultimately, their entry into the gut carbon cycle trigger metabolic reprogramming, reducing short-chain fatty acid production, disrupting energy homeostasis, and reallocating carbon flux. This led to suppressed host feeding behavior and significant weight loss.

“This work comprehensively maps the dynamic biotransformation pathways of biodegradable microplastics within mice. It 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," said Prof. CHEN Chunying.