Perfluorooctanoic acid exposure disrupts gut microbiota and aggravates experimental colitis

Area of Science:

• Environmental Health
• Gastroenterology
• Toxicology

Background:

• Perfluorooctanoic acid (PFOA) is an persistent environmental contaminant linked to inflammatory bowel disease (IBD).
• Mechanisms of PFOA's impact on colonic inflammation during colitis are not fully understood.

Purpose of the Study:

• To investigate the effects of dietary PFOA exposure on dextran sulfate sodium (DSS)-induced colitis severity.
• To elucidate the underlying mechanisms of PFOA-induced exacerbation of colitis.

Main Methods:

• Utilized a DSS-induced mouse model of colitis.
• Assessed colitis severity through body weight loss, colon length, and histopathology.
• Analyzed colonic neutrophil infiltration and activation markers.
• Evaluated epithelial barrier integrity markers (goblet cells, E-cadherin).
• Performed fecal microbiome and metabolomic analyses.

Main Results:

• Dietary PFOA exposure significantly exacerbated colitis, indicated by increased weight loss, colon shortening, and tissue damage.
• PFOA promoted neutrophil infiltration and activation in the colon.
• Goblet cell depletion and reduced E-cadherin expression were observed, suggesting epithelial barrier disruption.
• Fecal microbiome and metabolomic profiles were altered by PFOA exposure, correlating with inflammation.

Conclusions:

• Dietary PFOA exposure aggravates experimental colitis via neutrophil-driven inflammation, epithelial barrier compromise, and microbiome alterations.
• PFOA may act as an environmental factor exacerbating IBD.
• Findings provide mechanistic insights into PFOA's influence on host-microbiome interactions in colitis.