Microbiota Modulates Host Response to Dietary Gluten in NOD/DQ8 Mice.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals expressing the HLA-DQ2 or DQ8 genes. Dysbiosis has been described in patients with CD, but it is unknown whether these microbial changes are a CD-promoting factor. We therefore took a gnotobiotic approach to investigate the influence of the microbiota on host responses to gluten in adult NOD/DQ8 mice, a model of gluten-sensitivity. Both conventional specific pathogen free mice, which harbour opportunistic bacteria including Proteobacteria, and germ-free mice developed gluten-induced small intestinal inflammation, characterized by increased intraepithelial lymphocytes, decreased villous-to-crypt ratios, and gluten specific immune responses. However, mice colonized with a limited, defined microbiota devoid of opportunistic pathogens and Proteobacteria (altered Schaedler flora; ASF) were protected from gluten-induced small intestinal inflammation and gluten-specific immune responses. Protection in ASF-colonized mice was reversed by colonization with Pseudomonas aeruginosa, a member of the Proteobacteria phylum, isolated from the small intestine of an active CD patient. These results provide evidence of modulation of host responses to gluten by intestinal microbiota. The presence or absence of specific opportunistic pathogens may promote or prevent gluten-induced inflammation in a genetically susceptible host.