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

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.