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.

Daniel Agardh is on a scientific advisory board for Sanofi.

This work was funded by NIH with award number R01DK124581. Proposal title was Gut Viral and Bacterial Associations with Celiac Disease in the TEDDY Cohort. This project was led by Dr. Richard Lloyd, Baylor College of Medicine, 2020-2025.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional Review Boards of the Colorado Multiple Institutional Review Board, Medical College of Georgia Human Assurance Committee, Georgia Health Sciences University Human Assurance Committee, Georgia Regents University Institutional Review Board, Augusta University Institutional Review Board, University of Florida Health Center Institutional Review Board, Washington State Institutional Review Board, Western Institutional Review Board, and European Ethics Committee Boards of the Finnish Ethics Committee of the Hospital District of Southwest Finland, Bayerischen Landesarztekammer (Bavarian Medical Association) Ethics Committee, Regional Ethics Board in Lund, Lund University Committee for Continuing Ethical Review gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Processed microbiome data derived from human samples will be deposited at the time of peer-reviewed publication likely using DRYAD.