{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:27:38Z","timestamp":1787167658394,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>A higher intake of gluten during childhood is associated with increased risk of celiac disease, and the incidence of celiac disease peaks shortly after the time point when associations with higher gluten intake during the second and third year of life occur. Additional environmental factors are most likely necessary for celiac disease to develop. It is hypothesized that gastrointestinal infections increase gut permeability and exposure to gluten. Alternatively, infections may lead to gut dysbiosis and chronic inflammation, with leakage of self-antigens that mimic gluten peptides that leads to an autoimmune-like response. Different gluten interventions to prevent celiac disease have been proposed. Early clinical studies suggested an optimal time point introducing gluten between 4 and 6 months of age while the infant is being breastfed. However, later clinical trials on reduced gluten intake given to infants have shown no protection from celiac disease if gluten introduction was delayed or if gluten was introduced in small amounts during the child\u2019s first year of life. Still, more randomized clinical trials (RCTs) are warranted to answer the question if a reduced amount of gluten, not only at the time of introduction during infancy but also in a longer time frame, will prevent children at genetic risk from having lifelong celiac disease. It needs to be clarified whether dietary interventions are effective strategies to be proposed as future prevention of celiac disease in the general population. The present mini-review provides an overview of ongoing or completed RCTs that have focused on interventions during early childhood with the aim of preventing celiac disease.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1106564","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T02:46:41Z","timestamp":1677034001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Intervention strategies in early childhood to prevent celiac disease\u2014a mini-review"],"prefix":"10.3389","volume":"14","author":[{"given":"Carin","family":"Andr\u00e9n Aronsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Agardh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-031521-032634","article-title":"The immunobiology and pathogenesis of celiac disease","volume":"18","author":"Iversen","year":"2023","journal-title":"Annu Rev Pathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(92)91819-P","article-title":"Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue')","volume":"102","author":"Marsh","year":"1992","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S18","DOI":"10.1111\/apt.16840","article-title":"Review article: Diagnosis of coeliac disease: A perspective on current and future approaches","volume":"56","author":"Anderson","year":"2022","journal-title":"Alimentary Pharmacol Ther"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41572-018-0054-z","article-title":"Coeliac disease","volume":"5","author":"Lindfors","year":"2019","journal-title":"Nat Rev Dis Primers."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00552-z","article-title":"The global burden of coeliac disease: Opportunities and challenges","volume":"19","author":"Makharia","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","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":"New Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002056","article-title":"Incidence of pediatric celiac disease varies by region: Celiac disease varies by region","author":"Marisa","year":"2023","journal-title":"Am J Gastroenterol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1053\/j.gastro.2017.02.002","article-title":"High incidence of celiac disease in a long-term study of adolescents with susceptibility genotypes","volume":"152","author":"Liu","year":"2017","journal-title":"Gastroenterology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.3390\/ijms22042027","article-title":"A cumulative effect of food and viruses to trigger celiac disease (CD): A commentary on the recent literature","volume":"22","author":"Barone","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.287","article-title":"Infections and risk of celiac disease in childhood: A prospective nationwide cohort study","volume":"110","author":"Marild","year":"2015","journal-title":"Am J Gastroenterol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.672148","article-title":"Can celiac disease be prevented","volume":"12","author":"Auricchio","year":"2021","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1111\/apt.16787","article-title":"Review article: Epidemiology of coeliac disease","volume":"56","author":"Makharia","year":"2022","journal-title":"Alimentary Pharmacol Ther"},{"key":"B13","doi-asserted-by":"publisher","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 paediatrica."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001105","article-title":"Gluten introduction and the risk of coeliac disease. A position paper by the European society for paediatric gastroenterology, hepatology & nutrition","volume":"62","author":"Szajewska","year":"2016","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.10329","article-title":"Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk","volume":"322","author":"Andren Aronsson","year":"2019","journal-title":"JAMA"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000255","article-title":"Gluten intake and risk of celiac disease: Long-term follow-up of an At-risk birth cohort","volume":"114","author":"Marild","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000331","article-title":"Gluten intake in early childhood and risk of celiac disease in childhood: A nationwide cohort study","volume":"114","author":"Lund-Blix","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"B18","doi-asserted-by":"publisher","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":"B19","doi-asserted-by":"publisher","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":"New Engl J Med"},{"key":"B20","doi-asserted-by":"publisher","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":"New Engl J Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-2456","article-title":"Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: The BABYDIET study","volume":"34","author":"Hummel","year":"2011","journal-title":"Diabetes Care"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1208","article-title":"Timing of gluten introduction and islet autoimmunity in young children: Updated results from the BABYDIET study","volume":"37","author":"Beyerlein","year":"2014","journal-title":"Diabetes Care"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2020.2893","article-title":"Early gluten introduction and celiac disease in the EAT study: A prespecified analysis of the EAT randomized clinical trial","volume":"174","author":"Logan","year":"2020","journal-title":"JAMA pediatrics."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.3390\/nu11081925","article-title":"Effects of lactobacillus plantarum and lactobacillus paracasei on the peripheral immune response in children with celiac disease autoimmunity: A randomized, double-blind, placebo-controlled clinical trial","volume":"11","author":"Hakansson","year":"2019","journal-title":"Nutrients."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e328363e26e","article-title":"Modulation of gut barrier function in patients with obstructive jaundice using probiotic LP299v","volume":"25","author":"Jones","year":"2013","journal-title":"Eur J Gastroenterol hepatology."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12055","article-title":"Differential effect on cell-mediated immunity in human volunteers after intake of different lactobacilli","volume":"172","author":"Rask","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2008.01748.x","article-title":"Lactobacillus plantarum 299v reduces colonisation of clostridium difficile in critically ill patients treated with antibiotics","volume":"52","author":"Klarin","year":"2008","journal-title":"Acta Anaesthesiol Scand"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-019-02137-8","article-title":"Evaluation of the efficacy of Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 on aspects of common cold infections in children attending day care: a randomised, double-blind, placebo-controlled clinical study","volume":"59","author":"Lazou Ahr\u00e9n","year":"2020","journal-title":"Eur J Nutr"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2013a metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J BioMed Inform."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0617-x","article-title":"Temporal development of the gut microbiome in early childhood from the TEDDY study","volume":"562","author":"Stewart","year":"2018","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.3390\/nu11102375","article-title":"The gut microbiota in celiac disease and probiotics","volume":"11","author":"Chibbar","year":"2019","journal-title":"Nutrients"},{"key":"B32","doi-asserted-by":"publisher","first-page":"4630","DOI":"10.1038\/s41467-018-07019-x","article-title":"A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults","volume":"9","author":"Hansen","year":"2018","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2021.1840354","article-title":"Gut microbiota in celiac disease: Microbes, metabolites, pathways and therapeutics","volume":"16","author":"Olshan","year":"2020","journal-title":"Expert Rev Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.09.030","article-title":"Effects of gluten intake on risk of celiac disease: A case-control study on a Swedish birth cohort","volume":"14","author":"Aronsson","year":"2016","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319809","article-title":"Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children: The TEDDY study","volume":"69","author":"Lindfors","year":"2020","journal-title":"Gut"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/nu7115470","article-title":"Celiac disease genomic, environmental, microbiome, and metabolomic (CDGEMM) study design: Approach to the future of personalized prevention of celiac disease","volume":"7","author":"Leonard","year":"2015","journal-title":"Nutrients"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.116.144352","article-title":"The role of gluten consumption at an early age in celiac disease development: a further analysis of the prospective PreventCD cohort study","volume":"105","author":"Crespo-Escobar","year":"2017","journal-title":"Am J Clin Nutr"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.17235\/reed.2018.5324\/2017","article-title":"Ten years of follow-up of the Spanish cohort of the European PreventCD study: The lessons learned","volume":"110","author":"Crespo Escobar","year":"2018","journal-title":"Rev Esp Enferm Dig."},{"key":"B39","doi-asserted-by":"publisher","first-page":"5396","DOI":"10.1038\/s41598-022-09232-7","article-title":"Gluten consumption and inflammation affect the development of celiac disease in at-risk children","volume":"12","author":"Auricchio","year":"2022","journal-title":"Sci Rep"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00741.x","article-title":"Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study","volume":"101","author":"Stene","year":"2006","journal-title":"Am J Gastroenterol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.cgh.2016.10.033","article-title":"Factors that increase risk of celiac disease autoimmunity after a gastrointestinal infection in early life","volume":"15","author":"Kemppainen","year":"2017","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31818c52cc","article-title":"Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic","volume":"49","author":"Myleus","year":"2009","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document. the international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.3390\/nu12092674","article-title":"Probiotics, prebiotics and other dietary supplements for gut microbiota modulation in celiac disease patients","volume":"12","author":"Marasco","year":"2020","journal-title":"Nutrients"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1106564\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T02:46:44Z","timestamp":1677034004000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1106564\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,22]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2023.1106564"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1106564","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,22]]},"article-number":"1106564"}}