Researchers at the Mucosal Immunology and Biology Research Center (MIBRC) at Massachusetts General Hospital, led by Stefania Seger and CDF Medical Advisory Board member Alessio Fasano, have created 3-D, miniature models of the intestines—called intestinal organoids—in order to research celiac disease. Tissue taken from the intestinal biopsies of patients allowed for these “mini-guts” to be grown in vitro (in a test tube or culture dish) so that researchers could explore how the intestines of someone with celiac disease respond to gluten.
No animals respond to gluten the way that humans with celiac disease do, making research in this area difficult due to lack of animal testing availability and complications of testing this concept in humans. In order to examine the effect of gluten in people with celiac, patients must ingest gluten for up to 8 weeks—a painful and difficult task for someone with celiac disease. Because of this, it is difficult for researchers to find enough participants with celiac disease for studies that require ingestion of gluten without an investigational drug to reduce the negative effects. A method that allows the effect of gluten on the intestines of someone with celiac disease to be studied outside of the body, without causing any patient discomfort, could drastically change the way celiac disease research is conducted.
Earlier studies have shown that these intestinal organoids retain the genes of the tissue that they are taken from—including diseased tissue. This means that organoids with celiac disease will react to testing the same way that intestines inside a living person with celiac disease would. The study researchers discovered 472 genes in the celiac disease organoids that differed from organoids without celiac disease. These include genes associated with intestinal functions related to celiac disease, including gut barrier maintenance, stem cell regeneration, and immune response. Researchers also found that products created from intestinal cells can be used to modify the body’s response to gluten, which could lead to future treatment strategies.
Alessio Fasano, co-senior author on this study and director of the Mucosal Immunology and Biology Research Center states, “These results confirm our hypothesis that genes and exposure to gluten are necessary but not sufficient, since changes in both the composition and function of the gut microbiome are also needed to switch from genetic predisposition to clinical outcome, as shown by our data.”
According to co-senior author Stefania Seger, this research marks a major shift in the study of celiac disease, and further drug screenings could identify and develop new personalized treatments for patients with celiac disease. This could be an important step to an increased understanding of celiac disease, leading to better treatments and a cure.
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