Oral Presentation International Celiac Disease Symposium 2026

Improved gluten degradation by microbiota in the presence of Saccharomyces boulardii CNCM I-745 and Lactobacillus reuteri (144954)

Kelly R Kan 1 2 , Marco Constante 2 , Sara Rahmani 2 , Amy Russell 3 , Mitchell McInerney 4 , Gaston H Rueda 2 , Maria I Pinto-Sanchez 2 , Xavier Roux 5 , Premysl Bercik 2 , Ludvig M Sollid 6 , Joseph A Murray 7 , Jason A Tye-Din 3 8 9 , Anthony W Purcell 4 , Heather Galipeau 2 , Alberto Caminero 2 , Elena F. Verdu 2
  1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
  2. Department of Medicine, Farncombe Family Digestive Health Research Institute, Hamilton, ON, Canada
  3. Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC, Australia
  4. Department of Biochemistry and Molecular Biology and Immunity Program, Monash University, Clayton, VIC, Australia
  5. Microbiology Department, Biocodex, Compiègne, France
  6. Institute of Immunology, University of Oslo, Oslo, Norway
  7. Celiac Disease Program, Mayo Clinic, Rochester, Minnesota, United States
  8. Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
  9. Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC, Australia

Background: Gluten drives celiac disease (CeD) through immunogenic peptides that activate T cells in genetically susceptible individuals. Because gluten exposure is difficult to avoid and CeD-associated microbiota has reduced gluten-degrading capacity, enhancing cooperative microbial gluten metabolism could provide an adjunct to the gluten-free diet. The yeast probiotic Saccharomyces boulardii CNCM I-745 (S. boulardii) has been shown to enhance total protein degradation, suggesting that it may promote the breakdown of immunogenic gluten-derived peptides. We therefore investigated whether S. boulardii enhances gluten degradation and detoxification through interactions with small intestinal microbes.

Methods: Specific pathogen-free HLA-DQ2.5 knock-in and NOD/DQ8 mice received two oral gavages of S. boulardii (3 g/kg) or vehicle over 2 days, with the second inoculum administered together with a 20 mg gluten bolus. Gluten immunogenic peptides (GIPs) were quantified in small intestinal contents collected 4 hours after gluten administration using G12 ELISA. CeD patient-derived duodenal microbiota was cultured in Opti-MEM with synthetic immunodominant GIPs, with or without S. boulardii (1×106 CFU) and/or Lactobacillus reuteri (L. reuteri; 1×108 CFU). Peptide degradation was assessed by LC-MS detection of gluten-derived peptides, and detoxification was assessed using a disease-relevant IFN-γ ELISpot assay with gluten-specific T-cell clones (TCC) derived from peripheral blood samples of CeD patients.

Results: S. boulardii reduced small intestinal GIP concentrations in the HLA-DQ2.5 and NOD/DQ8 mice. In CeD patient-derived duodenal microbiota cultures with low lactobacilli abundance, the combination of S. boulardii and L. reuteri reduced GIP concentrations more than duodenal microbiota alone or either probiotic individually. The combination enhanced cleavage of the 33-mer peptide and gluten-derived peptides containing the glia-α1, glia-ω1, and Hor-3a immunodominant T-cell epitopes, and reduced IFN-γ production by CeD TCC compared with microbiota alone.

Conclusions: CeD-associated impairment of microbial gluten degradation can be improved by employing cooperative microbial metabolism, thus broadening therapeutic strategies beyond microbial or enzyme monotherapies.