A butyrate-succinate axis regulates tuft cell expansion and type II immunity 3911

Abstract Description A broad range of immunomodulatory activities have been attributed to butyrate, a short chain fatty acid produced by bacterial fermentation of dietary fiber in the distal gut. Previous work from our laboratory has implicated butyrate in protection against allergic responses to food. The Alenghat laboratory recently reported a new allergy-protective role for butyrate. They showed that butyrate constrains the differentiation of intestinal epithelial tuft cells. Tuft cells can sense succinate produced by helminths and protists to trigger the production of alarmins which initiate type II immunity. Succinate production by bacterial taxa has not been well studied. We have shown that germ-free mice colonized with the microbiota of cow’s milk allergic (CMA), but not healthy, infants exhibit an anaphylactic response to food upon allergen sensitization and challenge. We now report that, in addition to low concentrations of butyrate, mice colonized with the CMA microbiota have high concentrations of cecal succinate. After two rounds of allergen sensitization, tuft cell numbers are significantly expanded in the ileum of CMA, but not healthy, colonized mice. Preliminary data suggests that sensitization is required to increase tuft cell numbers; colonization with the CMA microbiota is not sufficient. We expect that this new focus will reveal novel pathways for therapeutic intervention that involve bacterial taxa highly specialized for both butyrate production and succinate consumption. Funding Sources Supported by NIH R01 AI146099; Food Allergy Fund. Topic Categories Mucosal and Regional Immunology (MUC)