Mechanistic Insights into Gut Microbial Contributions to Celiac Disease Pathogenesis

Celiac disease (CeD) is a common autoimmune disorder triggered by gluten in genetically susceptible individuals. Although up to 40% of the population carries risk alleles (HLA-DQ2/DQ8) for the disease, only 1–2% develop CeD. This indicates that environmental factors play a critical role — one such factor being the gut microbiome. Currently, the sole treatment is strict adherence to a gluten-free diet, which can be challenging and sometimes fails to fully resolve symptoms. These limitations highlight the need to better understand environmental factors contributing to CeD and develop therapies beyond dietary management.

Recent research at UMC Groningen (home institute) used high-resolution metagenomic sequencing of faecal samples from two large Dutch cohorts (259 treated CeD (tCeD) patients and 765 healthy controls) and revealed significant strain-level differences in the common gut bacterium Eubacterium rectale in individuals with tCeD. The enriched strains harboured genetic repertoires potentially involved in CeD through altered substrate processing and flagellum-mediated epithelial priming. Following in-depth in-vitro strain characterisation, and supported by a Mitacs grant and the expertise of the host institute, we aim to perform functional testing of Eubacterium rectale strains in specialised CeD mouse models to gain further mechanistic insights into their potential role in CeD pathogenesis.

Faculty Supervisor:

Elena Verdu

Student:

Partner:

University Medical Center Groningen

Discipline:

Life Sciences

Sector:

Health and Related Sciences & Technology

University:

McMaster University

Program: