The role of skin inflammation, barrier dysfunction, and oral tolerance in skin sensitization to gluten-derived hydrolysates in a rat model.

BACKGROUND: Adverse reactions to wheat-containing skin care products have been linked to food allergy development. OBJECTIVES: To determine the role of skin barrier dysfunction and inflammation in sensitization to gluten-derived hydrolysates via the skin in Brown Norway rats with and without oral tolerance to wheat. METHODS: Skin barrier defect was induced by mechanical disruption, and skin inflammation was induced by topical application of SLS or MC903. Unmodified, enzyme hydrolyzed, or acid hydrolyzed gluten products were applied to the skin three times per week for 5 weeks. Subsequently, rats were orally gavaged with unmodified gluten. RESULTS: Wheat-naïve rats were readily sensitized to gluten hydrolysates via the skin. Skin barrier defect and skin inflammation had little effect on the skin sensitization and hydrolysate-specific IgE levels. Oral administration of unmodified gluten promoted the production of unmodified gluten-specific IgE in rats sensitized via the skin. Sensitization through intact skin, disrupted skin barrier, or inflamed skin was unable to break tolerance to unmodified gluten in rats on a wheat-containing diet. CONCLUSIONS: Mechanical skin barrier disruption and skin inflammation play a limited role in experimental skin sensitization to gluten-derived hydrolysates.

Amoxicillin does not affect the development of cow's milk allergy in a Brown Norway rat model.

The use of antibiotics as well as changes in the gut microbiota have been linked to development of food allergy in childhood. It remains unknown whether administration of a single clinically relevant antibiotic directly promotes food allergy development when administrated during the sensitisation phase in an experimental animal model. We investigated whether the antibiotic amoxicillin affected gut microbiota composition, development of cow's milk allergy (CMA) and frequencies of allergic effector cells and regulatory T cells in the intestine. Brown Norway rats were given daily oral gavages of amoxicillin for six weeks and whey protein concentrate (WPC) with or without cholera toxin three times per week for the last five weeks. Microbiota composition in faeces and small intestine was analysed by 16S rRNA sequencing. The development of CMA was assessed by WPC-specific IgE in serum, ear swelling response to WPC and body hypothermia following oral gavage of WPC. Allergic effector cells were analysed by histology, and frequencies of regulatory and activated T cells were analysed by flow cytometry. Amoxicillin administration reduced faecal microbiota diversity, reduced the relative abundance of Firmicutes and increased the abundance of Bacteroidetes and Proteobacteria. Despite these effects, amoxicillin did not affect the development of CMA, nor the frequencies of allergic effector cells or regulatory T cells. Thus, amoxicillin does not carry a direct risk for food allergy development when administrated in an experimental model of allergic sensitisation to WPC via the gut. This finding suggests that confounding factors may better explain the epidemiological link between antibiotic use and food allergy.