4/1/2023 0 Comments Rarify scissors![]() BAs are categorized into two types: primary and secondary BAs. BAs also serve as important signaling molecules that regulate their own synthesis, and influence intestinal epithelial cell (IEC) health and immune cell function 20, 21, 22, 23, 24, 25. ![]() BAs are a diverse family of small amphipathic molecules that, through their detergent properties, promote the solubilization and absorption of dietary lipids and lipid-soluble vitamins from the gut lumen 19. One critical metabolic function carried out exclusively by bacteria in the gut is bio-transformation of host bile acids (BAs) 16, 17, 18. Under normal physiological conditions, bacterial metabolism in the gut has a profoundly positive influence on host physiology by promoting detoxification of harmful dietary compounds, limiting inflammatory immune responses, and enhancing the bioavailability of nutrients 8, 14, 15. The underlying mechanisms through which dysbiosis causes chronic inflammation are not well-defined. In antibody-deficient humans, the abnormal composition of the gut microbiota (‘dysbiosis’) is associated with chronic inflammatory responses 7, 11, 12, 13. Mouse models have been instrumental in demonstrating that mucosal antibodies (particularly immunoglobulin A) regulate the taxonomic composition 6, 7, metabolic output 8, and spatial organization 9, 10 of the gut microbiota. ![]() Collectively, results from our experiments support a model whereby mucosal humoral immune responses limit inflammatory disease of the small bowel by regulating bacterial BA metabolism.Īntibody-deficiency is the most common form of primary (i.e., heritable) immunodeficiency observed in humans, and gastrointestinal complications are commonly observed in antibody-deficient patients 1, 2, 3, 4, 5. Manipulation of bile acid availability, adoptive transfer of functional B cells, and ablation of bacterial bile salt hydrolase activity all influence the severity of small intestine enteropathy in CD19 −/− mice. ![]() The gluten-sensitive small intestine enteropathy that develops in CD19 −/− mice is associated with alterations to luminal bile acid composition in the SI, marked by significant reductions in the abundance of conjugated bile acids. Here, we use a CD19 −/− mouse model of antibody-deficiency to demonstrate that a relationship exists between dysbiosis, defects in bile acid homeostasis, and gluten-sensitive enteropathy of the small intestine. Whether and how mucosal antibody responses influence gut health through modulation of microbiota composition is unclear. Mucosal antibodies maintain gut homeostasis by promoting spatial segregation between host tissues and luminal microbes. ![]()
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