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

  • J Agric Food Chem. 2026 Feb 18;74(6):5718-5730. doi: 10.1021/acs.jafc.5c15484.
Chuxin Zhang  1 ,  Yitao Yan  2 ,  Xu Li  1 ,  Jiaxing An  1 ,  Wenjing Li  3 ,  Juan Shao  1 ,  Zhongyuan Guo  1
Affiliations
  • 1. School 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.
  • 2. The First Clinical Medical School, Shanxi Medical University, Taiyuan 030001, China.
  • 3. Academy of Medical Sciences, Shanxi Medical University, Jinzhong 030600, China.
PMID: 41657037 DOI: 10.1021/acs.jafc.5c15484
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.

Keywords
AMPK signaling; DNA damage; PET microplastics; intestinal barrier dysfunction; mitochondrial dysfunction.
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