Urolithin A attenuates arsenic-induced gut barrier dysfunction

Area of Science:

• Environmental Toxicology
• Gut Microbiome Research
• Cellular Biology

Background:

• Environmental chemicals like inorganic arsenic (iAs) induce redox toxicity and oxidative stress, disrupting gut homeostasis and intestinal barrier integrity.
• Gut microbiota play a protective role against iAs toxicity, but the specific impact of microbial metabolites on iAs-induced gut damage remains unclear.

Purpose of the Study:

• To investigate the impact of inorganic arsenic (iAs) on gut barrier function.
• To determine the protective benefits of the gut microbial metabolite urolithin A (UroA) against iAs-induced damage to the gut epithelium.

Main Methods:

• Utilized colon epithelial cells and a human intestinal 3D organoid model system.
• Investigated iAs-induced cell toxicity, oxidative stress, and gut barrier dysfunction with and without UroA treatment.

Main Results:

• Urolithin A (UroA) treatment attenuated iAs-induced cell toxicity, apoptosis, and oxidative stress in colon epithelial cells.
• UroA significantly reduced iAs-induced gut barrier permeability and inflammatory markers in both cell and organoid models.
• Mechanistically, UroA protected against iAs-induced disruption of tight junctional proteins by blocking oxidative stress and inflammation.

Conclusions:

• Microbial metabolites, specifically urolithin A (UroA), show potential in protecting against environmental hazards like inorganic arsenic (iAs).
• UroA enhances gut barrier function and reduces intestinal oxidative stress, offering a novel therapeutic avenue.