Defective humoral immunity disrupts bile acid homeostasis which promotes inflammatory disease of the small bowel.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35082296.
- Also identified by DOI 10.1038/s41467-022-28126-w and PMC identifier 8792037.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-/-</sup> 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<sup>-/-</sup> 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<sup>-/-</sup> 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.
Medical subject headings
- Bile Acids and Salts
- Homeostasis
- Immunity, Humoral
- Inflammatory Bowel Diseases
- Intestine, Small