Abstract
Longitudinal study of the microbial dysbiosis preceding celiac disease (CD) is needed, particularly in the first several years of life. Within the Environmental Determinants of Diabetes in the Young (TEDDY) multi-national prospective cohort study, a case-cohort study of 306 CD cases (i.e., seroconverting by 48 months of age), with controls matched 2:1 by site, gender, and time of birth, was assessed. Temporal microbiome case-control dynamics were modelled by 16S rRNA analysis of monthly sequential stool samples taken from age three months up to age four (or until the development of CD). Significant differences were identified across time, including key taxa that break down gluten and influence inflammation, all before the development of autoantibodies. Key bacterial associations with environmental factors such as diet were assessed using detailed longitudinal nutrient intake and diary data, along with genetic variants conferring high CD risk.