Ascorbate exacerbates iron toxicity on intestinal barrier function against Salmonella infection

Area of Science:

• Nutrition Science
• Microbiology
• Cell Biology

Background:

• Ascorbic acid enhances iron absorption but can have pro-oxidant effects.
• Iron supplementation is common, but its interaction with ascorbic acid regarding gut health is unclear.

Purpose of the Study:

• To investigate the role of ascorbic acid in iron toxicity on intestinal resistance against foodborne pathogens.
• To evaluate the impact of iron-ascorbate co-treatment on intestinal epithelial barrier function and Salmonella Typhimurium infection.

Main Methods:

• Utilized polarized Caco-2 cell monolayers and Salmonella Typhimurium infection models.
• Assessed cell viability, membrane integrity, paracellular permeability, and oxidative stress markers.
• Evaluated effects in Salmonella-infected C57BL/6 mice, measuring body weight, survival, colon length, and pathogen colonization.

Main Results:

• Iron-ascorbate co-treatment significantly increased Salmonella adhesion, invasion, and translocation compared to iron alone.
• Impaired cell viability, membrane integrity, and paracellular permeability were observed with iron-ascorbate co-treatment.
• In vivo studies showed exacerbated weight loss, reduced survival, and increased gut damage and pathogen load in iron-ascorbate supplemented mice.

Conclusions:

• Ascorbic acid exacerbates iron toxicity, compromising intestinal barrier function and increasing susceptibility to Salmonella infection.
• The pro-oxidant effects of iron-ascorbate impair the intestinal epithelial barrier and facilitate pathogen colonization.
• Antioxidant treatment (butylated hydroxytoluene) mitigated the toxic effects, highlighting the role of oxidative stress.