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Gluten-free diet exposure prohibits pathobiont expansion and gluten sensitive enteropathy in B cell deficient mice

Citation

Kubinak, Jason (2021), Gluten-free diet exposure prohibits pathobiont expansion and gluten sensitive enteropathy in B cell deficient mice, Dryad, Dataset, https://doi.org/10.5061/dryad.v9s4mw6xb

Abstract

In humans, celiac disease (CeD) is a T-cell-driven gluten-sensitive enteropathy (GSE) localized to the small bowel (duodenum). The presence of antibodies specific for gluten- and self-antigens are commonly used diagnostic biomarkers of CeD and are considered to play a role in GSE pathogenesis. Previously, we have described an apparent T-cell-mediated GSE in CD19-/- mice, which develop weak and abnormal B cell responses. Here, we expand on this observation and use a mouse model of complete B cell deficiency (JH-/- mice), to show that absence of a humoral immune response also promotes development of a GSE. Furthermore, 16S analysis of microbial communities in the small intestine (SI) demonstrates that a gluten-free diet (GFD) suppresses the expansion of anaerobic bacteria in the SI and colonization of the SI by a specific pathobiont. Finally, we also observe that SI enteropathy in mice fed a gluten-rich diet (GRD) is positively correlated with the abundance of several microbial peptidase genes, which supports that bacterial metabolism of gluten may be an important driver of GSE in our model. Collectively, results from our experiments indicate that JH-/- mice will be a useful resource to investigators seeking to empirically delineate the contribution of humoral immunity on GSE pathogenesis, and support the hypothesis that humoral immunity promotes tolerance to gluten.

Methods

The datasets represent the raw data collected and used to generate the main figures associated with this manuscript. Data was analyzed as detailed in the published manuscript.

Usage Notes

Data pertaining to supplementary datasets can be made available upon reasonable request made to corresponding author.

Funding

NIH, Award: R01AI155887

NIH, Award: R21AI142409

NIH, Award: P20GM103641 (awarded to Prakash and Mitzi Nagarkatti)