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Foodborne PET Microplastic Contamination Compromises Intestinal Barrier through a Mitochondrial-AMPK-DNA Damage Pathway

Journal of Agricultural and Food Chemistry 2026
Chuxin Zhang, Yitao Yan, Li Xu, Jiaxing An, Wenjing Li, Juan Shao, Juan Shao, Zhongyuan Guo

Summary

Researchers evaluated the toxicity of gastrointestinal-digested PET microplastics in a human intestinal cell model and found they triggered oxidative stress, barrier disruption, and inflammatory cytokine dysregulation. Metabolomic analysis revealed that the damage occurred through a mitochondrial-AMPK-DNA damage pathway. The study suggests that foodborne PET microplastics may compromise intestinal barrier integrity through specific molecular mechanisms.

Polymers

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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