Celiac dysbiosis does not transcend geographic boundaries

Abstract

ABSTRACTCeliac disease is an autoimmune disorder of the small intestine in which gluten, an energy-storage protein found in wheat and other cereals, elicits an immune response that leads to villous atrophy. Despite a strong genetic component, celiac disease arises sporadically and at any age, leading us to hypothesize that changes in the microbiome influence celiac disease development and/or progression. Here, we pooled and computationally analyzed 16S data from 3 prior international studies that examined celiac disease and the microbiome. For our analysis, we combined the dada2 and PICRUSt 2 pipelines and a variety of data transformations that control for batch effects to determine whether any taxonomic or metabolic features were consistently associated with the celiac microbiome across the globe. Our results showed the celiac microbiome displays dysbiosis without a discernable pattern, which suggests perturbations in the celiac microbiome are a result of the disease rather than a cause. Data from PICRUSt 2 supported this conclusion and revealed connections between celiac disease and the metabolome that are supported by previous research examining dysbiotic microbiomes.IMPORTANCECeliac disease is an autoimmune disorder that affects roughly 2% of the world’s population. Although the ultimate cause of celiac disease is unknown, many researchers hypothesize that changes to the intestinal microbiome play a key role in disease progression. If this is the case, it may be possible to design therapies that manipulate the microbiome to suppress celiac disease. Here, we analyzed pooled data from 3 different studies from across the globe that examined celiac disease and the microbiome to ascertain whether there exists a unique celiac microbiome that transcends geographic boundaries.