TY - JOUR
T1 - Defective humoral immunity disrupts bile acid homeostasis which promotes inflammatory disease of the small bowel
AU - Mohammed, Ahmed Dawood
AU - Mohammed, Zahraa
AU - Roland, Mary M.
AU - Chatzistamou, Ioulia
AU - Jolly, Amy
AU - Schoettmer, Lillian M.
AU - Arroyo, Mireya
AU - Kakar, Khadija
AU - Tian, Yuan
AU - Patterson, Andrew
AU - Nagarkatti, Mitzi
AU - Nagarkatti, Prakash
AU - Kubinak, Jason L.
N1 - Funding Information:
J.L.K. was supported by a NIAID K22 Award (AI123481), a Jeffrey Modell Network Specific Diseases Research Award, a University of South Carolina ASPIRE-I Award, a pilot project award through the University of South Carolina Center for Alternative Medicine COBRE program (P20GM103641; awarded to Drs. Mitzi and Prakash Nagarkatti), an R21 (AI142409), and 1R01AI155887. A.D.M. was supported by the Iraqi Government through participation in the MOHESR Program. We would like to thank Dr. Sloan Devlin and Dr. Lina Yao for graciously providing the WT B.theta and Δbsh-B.theta strains developed in her lab for use in our experiments, as well as for providing useful comments during revision of this manuscript. We would like to thank members of the USC Genomics Core Dr. Misha Shtutman and Hao (Emily) Ji for their assistance in RNAseq experiments and analyses.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-28126-w
DO - 10.1038/s41467-022-28126-w
M3 - Article
C2 - 35082296
AN - SCOPUS:85123571121
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 525
ER -