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

Abstract

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.

NAD + precursors and bile acid sequestration treat preclinical refractory environmental enteric dysfunction

“…Although our data do not support the claim that LPD consumption lowers cecal SCFA or IgA, it is worth noting that cholestyramine treatment could potentially induce these changes. Cholestyramine worsens enteropathy in a CD19 knockout mouse model of gluten-sensitive enteropathy, which exhibits partial overlap in histopathology with EED ( 79 ). Therefore, additional studies may be warranted in translating these findings to clinical practice.…”

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis

“…Bile acids were physiological detergents that facilitate excretion, absorption, and transport of fats, sterols and other hydrophobic nutrients in the intestine and liver ( Claudel et al., 2005 ). They stimulate bile flow and intestinal motility, regulate lipid secretion and glucose levels, which are essential for the solubilization and absorption of dietary lipids and fat-soluble vitamins ( Keely et al., 2022 ; Mohammed et al., 2022 ). It has been implicated in the regulation of all the key enzymes for cholesterol homeostasis.…”

Bile acids as modulators of gut microbiota composition and function

“… 103 Finally, B cells produce mucosal antibodies shaping the gut microbiota. 104 Abbreviations: cAMP, Cyclic adenosine monophosphate; CREB, cAMP response element-binding protein; FXR, farnesoid X receptor; IL, interleukin; MDR1, Multidrug Resistance Protein 1; NF-κB, nuclear factor-kappa B; NLRP3, Nod-like receptor family pyrin domain containing 3; PKA, protein kinase A; PXR, pregnane X receptor; RORγt, retinoic acid-related orphan receptor gamma t; ROS, reactive oxygen species; SCFA, short-chain fatty acids; SHP, small heterodimer partner; TGR5, Takeda G protein-coupled receptor 5; T H , T helper cell; TLR4, Toll-like receptor 4; T reg , regulatory T cell; VDR, vitamin D receptor. Created with BioRender.com.…”

“…B cell deficiency perturbs ileal bsh activity of the microbiota, thus altering the bile acid composition in the gut and favoring the development of an ileal enteropathy ( Figure 4 ). 104 …”