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Dryad

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

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Nov 16, 2021 version files 87.86 KB

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.