Mechanism of Turicibacter-mediated metabolic protection and influence of mucosal immunity over its colonization 3424

Abstract Description Globally, metabolic syndrome affects 25% of the population, causing health complications like cardiovascular disease, type II diabetes, and death. A key characteristic is accumulating excess ceramides. The commensal bacteria Turicibacter confers leanness in mice predisposed for obesity and decreases host production of ceramides, triglycerides, and lipid metabolism enzymes. When treated with extracted Turicibacter lipids while on a high fat diet, they maintain a healthy weight and metabolic protection. The direct mechanism of how Turicibacter-produced lipids provide this protection is still unknown. Little is known about Turicibacter and host immune activation either. Immunoglobulin A (IgA) aids in microbial regulation. IgA selectivity, influenced by T follicular helper (Tfh) cell activation, can increase epithelial adherence and colonization for key microbes. What activates Tfh cells to influence production of IgA selective for Turicibacter and maintenance of its colonization is unknown. When pattern recognition receptor signaling is altered specifically in T cells, levels of IgA and Tfh cells decrease in Peyer’s Patches, Turicibacter colonization is lost, and these mice become spontaneously obese. In this experimental proposal, I hypothesize that Turicibacter produces a metabolite that confers protection via alteration of the host’s ceramide synthesis pathway and lipid uptake, and that Turicibacter requires IgA presence for sufficient colonization to provide this benefit. Topic Categories Mucosal and Regional Immunology (MUC)