Elucidating the role of microbes in celiac disease through gnotobiotic modeling.

Abstract

Celiac disease (CeD) is a common immune-mediated disease triggered by the ingestion of gluten in genetically predisposed individuals. CeD is unique in that the trigger (gluten), necessary genes (HLA-DQ2 and DQ8), and the autoantigen (tissue transglutaminase) have been identified, allowing additional environmental co-factors, like the intestinal microbiota, to be studied through relevant in vivo models. Murine models for CeD have come a long way in the past decade and there are now in vitro and in vivo tools available that mimic certain aspects of clinical disease. These models, many of which express the CeD risk genes, have recently been used to study the mechanisms through which the microbiota play a role in CeD pathogenesis through a gnotobiotic approach. Historically, the generation of gnotobiology technology in mid-20th century allowed for the study of immunity and physiology under a complete absence of microbes (axenic) or known colonized status (gnotobiotic). This enabled understanding of mechanisms by which certain bacteria contribute to health and disease. With this perspective, here, we will discuss the various murine models currently being used to study CeD. We will then describe how utilizing axenic and gnotobiotic CeD models has increased our understanding of how microbes influence relevant steps of CeD pathogenesis, and explain key methodology involved in axenic and gnotobiotic modeling.