{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:56:54Z","timestamp":1790139414585,"version":"4.0.1"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,11]],"date-time":"2015-11-11T00:00:00Z","timestamp":1447200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006628","name":"Mead Johnson Nutrition","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006628","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007299","name":"Harvard Catalyst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007299","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Ellison Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/nu7115470","type":"journal-article","created":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T03:46:55Z","timestamp":1447300015000},"page":"9325-9336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic (CDGEMM) Study Design: Approach to the Future of Personalized Prevention of Celiac Disease"],"prefix":"10.3390","volume":"7","author":[{"given":"Maureen","family":"Leonard","sequence":"first","affiliation":[{"name":"Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Camhi","sequence":"additional","affiliation":[{"name":"Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Huedo-Medina","sequence":"additional","affiliation":[{"name":"Allied Health Sciences Department, University of Connecticut, Storrs, CT 06269, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[{"name":"Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1056\/NEJMra071600","article-title":"Celiac disease","volume":"357","author":"Green","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3109\/07853890.2010.514285","article-title":"Natural history of celiac disease autoimmunity in a USA cohort followed since 1974","volume":"42","author":"Catassi","year":"2010","journal-title":"Ann. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e33387","DOI":"10.1371\/journal.pone.0033387","article-title":"Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants","volume":"7","author":"Sellitto","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e177","DOI":"10.1371\/journal.pbio.0050177","article-title":"Development of the human infant intestinal microbiota","volume":"5","author":"Palmer","year":"2007","journal-title":"PLoS Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1056\/NEJMoa1400697","article-title":"Introduction of gluten, HLA status, and the risk of celiac disease in children","volume":"371","author":"Lionetti","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1056\/NEJMoa1404172","article-title":"Randomized feeding intervention in infants at high risk for celiac disease","volume":"371","author":"Vriezinga","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e1433","DOI":"10.1542\/peds.2009-2260","article-title":"Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children","volume":"125","author":"Decker","year":"2010","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.cgh.2014.10.012","article-title":"Perinatal risk factors for development of celiac disease in children, base on the propsective norwegian mother and child cohort study","volume":"13","author":"Emilsson","year":"2015","journal-title":"Clin. Gastroenterol. Hepataol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1111\/apt.13163","article-title":"Systematic review with meta-analysis: Early infant feeding and coeliac disease\u2014Update 2015","volume":"41","author":"Szajewska","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Canova, C., Zabeo, V., Pitter, G., Romor, P., Baldovin, T., Zanotti, R., and Simonato, L. (2014). Association of maternal education, early infections, and antibiotic use with celiac disease: A population-based birth cohort study in northeastern Italy. Am. J. Epidemiol., 180.","DOI":"10.1093\/aje\/kwu101"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1056\/NEJMoa1313977","article-title":"Risk of pediatric celiac disease according to HLA haplotype and country","volume":"371","author":"Liu","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1136\/gutjnl-2014-306931","article-title":"The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease","volume":"64","author":"Olivares","year":"2015","journal-title":"Gut"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/1756-0500-7-204","article-title":"Feasibility of self-collection of fecal specimens by randomly sampled women for health-related studies of the gut microbiome","volume":"7","author":"Feigelson","year":"2014","journal-title":"BMC Res. Notes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.amjmed.2010.02.019","article-title":"Celiac disease diagnosis: Simple rules are better than complicated algorithms","volume":"123","author":"Catassi","year":"2010","journal-title":"Am. J. Med."},{"key":"ref_15","unstructured":"Division of Nutrition, Physical Activity, and Obesity, National Center for Chronic Disease Prevention and Health Promotion Infant Feeding Practices II, Available online:http:\/\/www.cdc.gov\/nccdphp\/dnpao\/index.html."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e0134802","DOI":"10.1371\/journal.pone.0134802","article-title":"Methods for Improving Human Gut Microbiome Data by Reducing Variability through Sample Processing and Storage of Stool","volume":"10","author":"Gorzelak","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1093\/ije\/dyl170","article-title":"Cohort profile: The norwegian mother and child cohort study (NoBa)","volume":"35","author":"Magnus","year":"2006","journal-title":"Int. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1651-2227.2000.tb01210.x","article-title":"Epidemic of coeliac disease in Swedish children","volume":"89","author":"Ivarsson","year":"2000","journal-title":"Acta Paediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11971","DOI":"10.1073\/pnas.1002601107","article-title":"Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns","volume":"107","author":"Costello","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Marlid, K., Weimin, Y., Lebwohl, B., Green, P.H.R., Blaser, M.J., Card, T., and Ludvigsson, J.F. (2013). Antibiotic exposure and the development of coeliac disease: A nationwide case-control study. BMC Gastroenterol., 13.","DOI":"10.1186\/1471-230X-13-109"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.cell.2014.05.052","article-title":"Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences","volume":"158","author":"Cox","year":"2014","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11121-008-0109-6","article-title":"A general model for testing mediation and moderation effects","volume":"10","author":"Fairchild","year":"2009","journal-title":"Prev. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"435078:1","DOI":"10.1155\/2011\/435078","article-title":"The use of mixed models for the analysis of mediated data with time-dependent predictors","volume":"2011","author":"Blood","year":"2011","journal-title":"J. Environ. Public Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1037\/0022-3514.51.6.1173","article-title":"The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations","volume":"51","author":"Baron","year":"1986","journal-title":"J. Pers. Soc. Psychol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1037\/1082-989X.8.2.115","article-title":"Lower level mediation in multilevel models","volume":"8","author":"Kenny","year":"2003","journal-title":"Psychol. Methods"},{"key":"ref_26","unstructured":"US Department of Health and Human Services, National Institutes of Health National Institute of Allergy and Infectious Diseases. Progress in Autoimmune Diseases Research; 2005, Available online:http:\/\/www.niaid.nih.gov\/topics\/autoimmune\/Documents\/adccfinal.pdf."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/7\/11\/5470\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:51:51Z","timestamp":1760215911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/7\/11\/5470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,11]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2015,11]]}},"alternative-id":["nu7115470"],"URL":"https:\/\/doi.org\/10.3390\/nu7115470","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,11]]}}}