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

Ahmed Dawood Mohammed, Zahraa Mohammed, Mary M. Roland, Ioulia Chatzistamou, Amy Jolly, Lillian M. Schoettmer, Mireya Arroyo, Khadija Kakar, Yuan Tian, Andrew Patterson, Mitzi Nagarkatti, Prakash Nagarkatti, Jason L. Kubinak

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Article number525
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General
  • General Physics and Astronomy

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