Gastrointestinal Incomplete Degradation Exacerbates Neurotoxic Effects of PLA Microplastics via Oligomer Nanoplastics Formation

Abstract

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28‐day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease‐like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU‐i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.

Abstract

Polylactic acid (PLA) polymer and oligomer microplastics (MPs) degrade incompletely and completely in mice's gastrointestinal tract, respectively. Incomplete degradation of PLA polymer MPs increases their bioavailability, transforming them into oligomer nanoplastics (NPs). Both types of MPs induce PD‐like neurotoxicity by causing mitochondrial calcium overload in midbrain neurons. Notably, PLA oligomer MPs provoke a more significant neurotoxic response.