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Intestinal Organoids Expressing Celiac Disease Respond Differently to Gluten Exposure

In This Article

  • Researchers exposed intestinal organoids derived from tissue with celiac disease to gliadin, a main component of gluten
  • They identified 472 genes in celiac tissue that respond differently to gliadin exposure
  • The validation of the organoid model for celiac disease research marks a major shift in the study of the disease

Researchers at the Mucosal Immunology and Biology Research Center (MIBRC) at Massachusetts General Hospital have validated the use of intestinal organoids as faithful models for celiac disease.

Researchers exposed intestinal organoids derived from the tissue of celiac and non-celiac patients to gliadin, a main component of gluten. They identified 472 genes that were regulated differently in organoids reflecting celiac disease than in models without the disease.

The 3D models, also called "mini-guts," offer opportunities to observe in vitro the reactions of gut epithelium and microbiota-derived molecules to gluten, which is a trigger for patients who are genetically predisposed to celiac disease.

RNA sequencing has previously shown that intestinal organoids retain a gene expression that recapitulates the expression of their tissue of origin, including a diseased state. In a study, co-authored by Stefania Senger, PhD, developmental biologist at Mass General, and Alessio Fasano, MD, director of the Mucosal Immunology and Biology Research Center, further validated the organoid model for use in celiac disease research.

Dr. Senger said that while there are no animal models that recapitulate human responses to gliadin, intestinal organoids express the same molecular markers as actual epithelium in celiac tissue, thus providing a basis for study.

Dr. Senger remarked that the results of this research mark a major shift in the study of celiac disease, and that further drug screenings could identify and develop new, personalized treatments for patients with the disease.

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