From Exposure to Dysfunction: The Intestinal Toxicity of Per- and Polyfluoroalkyl Substances

Area of Science:

• Environmental Health
• Toxicology
• Gastroenterology

Background:

• Per- and Polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals with growing evidence linking them to adverse health effects.
• The gastrointestinal tract is a primary site for PFAS exposure and a target for their toxic effects.

Purpose of the Study:

• To review and integrate current evidence on the mechanisms by which PFAS impact intestinal homeostasis.
• To identify key knowledge gaps and suggest future research directions for PFAS-related gastrointestinal toxicity.

Main Methods:

• Literature review synthesizing updated evidence on PFAS effects on the gastrointestinal tract.
• Focus on structural, metabolic, and immunological mechanisms of PFAS toxicity.
• Analysis of PFAS impact on epithelial integrity, metabolic reprogramming, and gut microbiota.

Main Results:

• PFAS disrupt epithelial barrier function by down-regulating tight-junction proteins and inducing oxidative stress.
• PFAS alter gut microbial composition (dysbiosis) and host metabolic pathways.
• These disruptions activate inflammasome signaling, contributing to chronic inflammation.

Conclusions:

• PFAS exposure compromises intestinal homeostasis through multiple interconnected mechanisms.
• These effects link environmental PFAS exposure to chronic intestinal inflammation, inflammatory bowel disease, and metabolic disorders.
• Further integrative research is needed to refine human risk assessment and develop interventions.