A nutrient deficient, humanized diet drives immunoglobulin A overproduction in mice 2934

Abstract Description Undernutrition and growth stunting present a major global health challenge, with broad impacts on immunity in stunted individuals. This condition is multifactorial and arises due to a combination of poor diet, infection, and disruption of the intestinal microbiota. Immunoglobulin A (IgA) is a key regulator of the microbiota, and alterations in IgA production and microbial targeting have been demonstrated in undernourished children. However, due to the multifactorial nature of the disease, the mechanistic basis for this increase in IgA is unclear. To test the specific effects of a malnourished diet alone on intestinal IgA responses, we fed young SPF mice a macro-and-micronutrient deficient diet modeled after a malnourished human diet (named “Malawi-8” or “M8” diet). After 4 weeks of diet treatment, M8-fed mice had elevated small intestine luminal and serum IgA and higher proportions of intestinal IgA+ plasma cells relative to controls. Antibiotics reduced IgA levels in these mice, and preliminary 16s rRNA gene sequencing revealed that the M8 diet alters microbiota composition, driving the hypothesis that undernutrition promotes an immunogenic microbiota, which could contribute to intestinal inflammation in undernourished humans. Key future directions to understand the IgA-microbiota relationship during undernutrition include examining the antigen specificity of M8-induced IgA and identifying microbes of interest that could drive increased IgA during undernutrition. Topic Categories Mucosal and Regional Immunology (MUC)