Oral Presentation International Celiac Disease Symposium 2026

Functional Insights into Agathobacter rectalis Strain-Level Variation in Celiac Disease (#29)

Hanna Simpson 1 , Sara Rahmani 2 , Jelle Slager 1 , Alan Walker 3 , Elena F. Verdu 2 , Sebo Withoff 1 , Iris Jonkers 1
  1. University Medical Center Groningen, Groningen, GRONINGEN, Netherlands
  2. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  3. School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, North East Scotland, Scotland

Genetic susceptibility and gluten exposure are both required for celiac disease (CeD), yet only 30–40% of genetically predisposed individuals develop CeD1, suggesting additional environmental factors, including the gut microbiome, may contribute to disease onset. CeD has been consistently associated with altered gut microbiome composition 2-6, although mechanistic studies using representative model systems remain limited.

In a recent large-scale shotgun metagenomic analysis of faecal samples from two Dutch cohorts—the  Celiac Disease Northern Netherlands cohort (128 treated CeD patients [tCeD] and 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD and 654 controls)—we identified strain-level differences in Agathobacter rectalis (A. rectalis)7, formerly known as Eubacterium rectale. Notably, the immotile European subspecies, characterised by distinct metabolic potential and a lack of flagellin-encoding genes, was nearly absent in tCeD patients.

We hypothesise that strain-specific characteristics of  A. rectalis may influence CeD pathophysiology through flagellin-mediated epithelial priming and differences in substrate utilisation, including CeD-relevant carbon sources such as gluten, starch, and in combination thereof. To investigate this, we performed in vitro growth assays assessing substrate utilisation by different A.rectalis strains. Colony-forming unit (CFU) counts demonstrated strain-dependent growth on gluten- and starch-containing media, either as individual or combined carbon sources, potentially driven by differences in glycosyltransferase repertoires.

To investigate host-microbe interactions, we conducted pilot co-culture experiments using A. rectalis and human small intestinal epithelial monolayers. Co-culture with a flagellated A. rectalis strain resulted in reduced epithelial barrier integrity, supporting a potential role for bacterial motility in host responses. We are currently extending these findings in vivo by examining the effects of colonisation with several A. rectalis strains on CeD pathophysiology in NOD-DQ8 mice.

Our findings help deepen mechanistic insight into how strain-level variation within the gut microbiome may shape responses relevant to CeD.

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  6. Olivares M, Walker AW, Capilla A, Benítez-Páez A, Palau F, Parkhill J, Castillejo G, Sanz Y. Gut microbiota trajectory in early life may predict development of celiac disease. Microbiome. 2018;6(1):36. doi: 10.1186/s40168-018-0415-6.
  7. Slager, J., Simpson, H. L., Gacesa, R., Chen, L., Tan, I. L., Gelderloos, J., … Withoff, S. (2025). High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation. Gut Microbes, 17(1). https://doi-org.proxy-ub.rug.nl/10.1080/19490976.2025.2489071