title: Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic (CDGEMM) Study Design: Approach to the Future of Personalized Prevention of Celiac Disease.
abstract: In the past it was believed that genetic predisposition and exposure to gluten were necessary and sufficient to develop celiac disease (CD). Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli. Many environmental factors known to influence the composition of the intestinal microbiota are also suggested to play a role in the development of CD. These include birthing delivery mode, infant feeding, and antibiotic use. To date no large-scale longitudinal studies have defined if and how gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of CD in genetically-susceptible individuals. Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.
authors.affiliation: Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA. mleonard7@mgh.harvard.edu.|Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA 02114, USA. mleonard7@mgh.harvard.edu.
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Leonard
authors.affiliation: Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA. sscamhi@partners.org.|Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA 02114, USA. sscamhi@partners.org.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Camhi
authors.affiliation: Allied Health Sciences Department, University of Connecticut, Storrs, CT 06269, USA. tania.huedo-medina@uconn.edu.
authors.forename: Tania B
authors.initials: TB
authors.lastname: Huedo-Medina
authors.affiliation: Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA. afasano@mgh.harvard.edu.|Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA 02114, USA. afasano@mgh.harvard.edu.
authors.forename: Alessio
authors.initials: A
authors.lastname: Fasano
mesh_terms: D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology* / Q000517:prevention & control*; D019204:GTP-Binding Proteins / Q000097:blood; D000069196:Gastrointestinal Microbiome; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007422:Intestines / Q000382:microbiology; D008137:Longitudinal Studies; D055442:Metabolome; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires; D011503:Transglutaminases / Q000097:blood
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: celiac; cohort; design; environmental; genetic; gluten; metabolomic; microbiome; personalized medicine; prospective