Defective humoral immunity disrupts bile acid homeostasis which promotes inflammatory disease of the small bowel

Mucosal antibodies maintain gut homeostasis, and may influence gut health through modulation of microbiota composition. Here the authors use a CD19-deficient mouse model with deficient B-cell immune responses to uncover an association between humoral immunodeficiency, dysbiosis, and perturbations to bile acid homeostasis in the gut in the context of glute-sensitive enteropathy. Mucosal antibodies maintain gut homeostasis by promoting spatial segregation between host tissues and luminal microbes. Whether and how mucosal antibody responses influence gut health through modulation of microbiota composition is unclear. 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. 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. 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. 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.

Automated summary

Mucosal antibodies regulate bacterial bile acid metabolism to maintain gut homeostasis and limit the development of intestinal inflammatory diseases.