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Foodborne PET Microplastic Contamination Compromises Intestinal Barrier through a Mitochondrial-AMPK-DNA Damage
Chuxin Zhang1, Yitao Yan2, Xu Li1
1School of Forensic Medicine, Shanxi Medical University, Shanxi Key Laboratory of Forensic Medicine, and Key Laboratory of Forensic Toxicology, Ministry of Public Security, Jinzhong 030600, China.
Abstract:
Poly(ethylene terephthalate) microplastics (PET-MPs), prevalent dietary contaminants, pose potential risks to intestinal health; yet underlying mechanisms of sustained exposure remain poorly defined. We evaluated the toxicity of gastrointestinal-digested PET-MPs in a human intestinal epithelial coculture model for 24 h. Digested PET-MPs triggered cytotoxicity, oxidative stress, barrier disruption, and dysregulated cytokines, impairing epithelial homeostasis. Untargeted metabolomics identified the AMPK signaling pathway as a perturbed node. Functional validation confirmed that PET-MPs induced mitochondrial damage, resulting in ATP depletion and AMPK activation. This persistent activation mediated cellular proliferation arrest and DNA double-strand breaks. Critically, pharmacological inhibition of AMPK alleviated barrier defects and DNA damage. These results unveil a mitochondrial dysfunction-AMPK activation-DNA damage axis as a central mechanism in PET-MP-induced injury, providing mechanistic insight into the health risks of microplastic exposure.
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