More than ten years ago, Alessio Fasano, MD, conceived of a collaborative, prospective study to identify specific genetic, environmental and metabolomic factors in infants at risk of celiac disease. As newly appointed director of the Center for Celiac Research and Treatment at Mass General for Children (MGfC), Fasano had a goal of developing early interventions to prevent celiac disease—and autoimmunity—from developing by manipulating the gut microbiome. To do this, he would need to collect a lot of data to help solve the puzzle of when autoimmunity begins, so he assembled a team.

Maureen Leonard, MD, MMSc, a former fellow in the Department of Pediatric Gastroenterology and Nutrition at MGfC, joined Dr. Fasano’s team at the celiac center as clinical director in 2013 and became a collaborative partner in the longitudinal, multi-center Celiac Disease, Genomic, Environmental, Microbiome and Metabolome study (CDGEMM).

With the assistance of clinical research coordinator Victoria Kenyon and others, she has led the effort to collect extensive demographic and biological samples from 606 infants in the United States, Italy and Spain. To date, Leonard has received approximately 1.4 million in funding from the National Institute of Diabetes and Digestive and Kidney Diseases.

In 2019, Ali Zomorrodi, PhD, Computational Systems and Biology Lead, opened his lab as part of the celiac center to build computational, mechanistic models of the human microbiome to study how disease begins and, ultimately, to design personalized treatments.

The longitudinal analysis of more than 36,500 biospecimens and more than 145,500 clinical data points including environmental factors and genomic sequencing are bringing the group closer to solving the puzzle of when autoimmunity develops in early childhood and how to prevent it.

In a 2021 paper published in Proceedings of the National Academy of Sciences, Leonard,  et al. “uncovered several species, pathways, and metabolites, for which the abundance is significantly altered before CD onset compared to disease onset and which is distinct from results of matched controls.” Leonard, Fasano , Zomorrodi and collaborators have another paper in the pipeline that further elucidates microbial signatures prior to the development of autoimmunity and other factors influencing the development of celiac disease autoimmunity.

The celiac center team received some good news for the CDGEMM project at the end of August, when Dr. Fasano was awarded $822,642 from the National Institute of Allergy and Infectious Diseases to support CDGEMM research for FY 2023.

“Continued funding for this research is not only critical to solving the question of how a person tips from gluten tolerance to celiac disease, but also for understanding how autoimmune disorders develop in infants, children and adults,” says Fasano. “We’re in this for the long haul.”

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