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

Area of Science:

• Environmental Health
• Toxicology
• Cell Biology

Background:

• Poly(ethylene terephthalate) microplastics (PET-MPs) are common dietary contaminants.
• The mechanisms underlying PET-MP toxicity in the human gut are not well understood.

Purpose of the Study:

• To investigate the toxicity of gastrointestinal-digested PET-MPs on human intestinal epithelial cells.
• To elucidate the molecular mechanisms of PET-MP-induced intestinal injury.

Main Methods:

• Utilized a human intestinal epithelial coculture model exposed to digested PET-MPs for 24 hours.
• Performed untargeted metabolomics to identify perturbed cellular pathways.
• Conducted functional validation assays, including mitochondrial function tests and DNA damage assessments.
• Investigated the role of the AMPK signaling pathway and its inhibition.

Main Results:

• Digested PET-MPs induced cytotoxicity, oxidative stress, barrier disruption, and cytokine dysregulation.
• Metabolomics identified the AMPK signaling pathway as a key affected node.
• PET-MPs caused mitochondrial damage, leading to ATP depletion and subsequent AMPK activation.
• Activated AMPK mediated cell proliferation arrest and DNA double-strand breaks.
• Pharmacological inhibition of AMPK reduced barrier defects and DNA damage.

Conclusions:

• A novel mitochondrial dysfunction-AMPK activation-DNA damage axis is identified as a central mechanism in PET-MP-induced intestinal injury.
• These findings provide crucial mechanistic insights into the health risks associated with microplastic exposure.
• Targeting the AMPK pathway may offer a therapeutic strategy to mitigate microplastic-induced gut damage.