Human microbiota microbes Raw sequence reads

Celiac Disease (CD) is a gluten induced immune-mediated disease. Almost all CD patients possess human leukocyte antigens DQ2 or DQ8, however only small subset of individuals carrying these alleles develop CD. Despite tremendous efforts, the role of the environmental factors in CD pathogenesis remain unclear. In a retrospective longitudinal study, using samples representing all three phases of gut microbiota development (ages 1, 2.5 and 5), we identified significant differences in the composition and function of gut microbiota at each phase. Applying IgA-sequencing, we showed that children developing CD have more IgA coated bacteria and different bacterial targets of IgA compared to healthy controls. Further, pro-inflammatory metabolic pathways and inflammatory plasma metabolites were enriched in children developing CD. Our results define a potential link between proinflammatory gut microbiota composition and chronic inflammation in pre-CD. Targeting inflammatory bacteria in this critical window could affect the pathogenesis and prognosis of CD.