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

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.