{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:16:49Z","timestamp":1790709409600,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Disorders of gut\u2013brain interaction (DGBI) include a spectrum of disorders with chronic\/recurrent gastrointestinal symptoms, caused by dysregulation of microbiota\u2013gut\u2013brain interaction. Early-life events have been suggested as the main factors influencing the microbiota\u2013gut\u2013brain axis. We aimed to evaluate the prevalence of DGBI in 3-year-old children and its relationship with early-life events. Methods: The parents of children aged 3 years, who had been followed up in a well-baby clinic since they were 2 months old, were asked about any GI symptoms their child had experienced during the check-up visits between September 2023 and June 2024. The final diagnosis of DGBI was based on ROME IV criteria. Demographic data, including early-life factors, were collected. Results: Overall, 568 children (48.6% boys) were included, of whom 139 (24.5%) had symptoms consistent with at least one DGBI diagnosis. The most prevalent DGBI was functional constipation (20.4%), followed by colic (4.6%), infant regurgitation (2.8%), and dyschezia (1.6%). Approximately 48% of the children were breastfed for \u22656 months, and 21% were exposed to \u22651 antibiotic\/antiviral drugs in the first year of life. DGBI prevalence was significantly higher in girls than in boys (28.1% vs. 20.7%; p = 0.041). Exclusive breastfeeding was the most significant protective factor against DGBI, particularly if performed for \u22653 months. Conclusions: Sex was the most significant factor affecting DGBI prevalence in children aged \u22643 years; breastfeeding offers the most effective protection against DGBI development.<\/jats:p>","DOI":"10.3390\/children12111430","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T08:14:04Z","timestamp":1761207244000},"page":"1430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Early-Life Events and the Prevalence of Gut\u2013Brain Interaction Disorders in Children"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-4973","authenticated-orcid":false,"given":"Atchariya","family":"Chanpong","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0968-6415","authenticated-orcid":false,"given":"Natchayada","family":"Ponjorn","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9888-0565","authenticated-orcid":false,"given":"Nattaporn","family":"Tassanakijpanich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanlaya","family":"Koosakulchai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pornruedee","family":"Rachatawiriyakul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-3891","authenticated-orcid":false,"given":"Sirinthip","family":"Kittivisuit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puttichart","family":"Khantee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6428-2305","authenticated-orcid":false,"given":"Kamolwish","family":"Laoprasopwattana","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jena, A., Montoya, C.A., Mullaney, J.A., Dilger, R.N., Young, W., McNabb, W.C., and Roy, N.C. (2020). Gut-Brain Axis in the Early Postnatal Years of Life: A Developmental Perspective. Front. Integr. Neurosci., 14.","DOI":"10.3389\/fnint.2020.00044"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ratsika, A., Codagnone, M.C., O\u2019Mahony, S., Stanton, C., and Cryan, J.F. (2021). Priming for Life: Early Life Nutrition and the Microbiota-Gut-Brain Axis. Nutrients, 13.","DOI":"10.3390\/nu13020423"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.12703\/r\/11-7","article-title":"Recent Advances in Understanding the Roles of the Enteric Nervous System","volume":"11","author":"Chanpong","year":"2022","journal-title":"Fac. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"343ra81","DOI":"10.1126\/scitranslmed.aad0917","article-title":"Natural History of the Infant Gut Microbiome and Impact of Antibiotic Treatment on Bacterial Strain Diversity and Stability","volume":"8","author":"Yassour","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jcmgh.2019.04.009","article-title":"Neonatal Antibiotics Disrupt Motility and Enteric Neural Circuits in Mouse Colon","volume":"8","author":"Hung","year":"2019","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1136\/gutjnl-2012-303249","article-title":"Decreased Gut Microbiota Diversity, Delayed Bacteroidetes Colonisation and Reduced Th1 Responses in Infants Delivered by Caesarean Section","volume":"63","author":"Jakobsson","year":"2014","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1038\/s41467-019-09252-4","article-title":"Perinatal Factors Affect the Gut Microbiota up to Four Years after Birth","volume":"10","author":"Fouhy","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1002\/mnfr.201100124","article-title":"Breast Milk Contains Relevant Neurotrophic Factors and Cytokines for Enteric Nervous System Development","volume":"55","author":"Fichter","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41572-020-00222-5","article-title":"Paediatric Functional Abdominal Pain Disorders","volume":"6","author":"Thapar","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e001028","DOI":"10.1136\/bmjpo-2021-001028","article-title":"Early Life Antibiotics and Childhood Gastrointestinal Disorders: A Systematic Review","volume":"5","author":"Kamphorst","year":"2021","journal-title":"BMJ Paediatr. Open"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/nmo.12236","article-title":"Intestinal Microbiota Influence the Early Postnatal Development of the Enteric Nervous System","volume":"26","author":"Collins","year":"2014","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1113\/jphysiol.2010.197707","article-title":"Morphological and Functional Changes in Guinea-Pig Neurons Projecting to the Ileal Mucosa at Early Stages after Inflammatory Damage","volume":"589","author":"Nurgali","year":"2011","journal-title":"J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pensabene, L., Salvatore, S., D\u2019Auria, E., Parisi, F., Concolino, D., Borrelli, O., Thapar, N., Staiano, A., Vandenplas, Y., and Saps, M. (2018). Cow\u2019s Milk Protein Allergy in Infancy: A Risk Factor for Functional Gastrointestinal Disorders in Children?. Nutrients, 10.","DOI":"10.3390\/nu10111716"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1113\/jphysiol.2004.063388","article-title":"Postnatal Microbial Colonization Programs the Hypothalamic-Pituitary-Adrenal System for Stress Response in Mice","volume":"558","author":"Sudo","year":"2004","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Usui, N., Matsuzaki, H., and Shimada, S. (2021). Characterization of Early Life Stress-Affected Gut Microbiota. Brain Sci., 11.","DOI":"10.3390\/brainsci11070913"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2401939","DOI":"10.1080\/19490976.2024.2401939","article-title":"Gut Microbiota Mediate Early Life Stress-Induced Social Dysfunction and Anxiety-Like Behaviors by Impairing Amino Acid Transport at the Gut","volume":"16","author":"Zhu","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_17","unstructured":"Kelsey, J.L., Whittemore, A.S., Evans, A.S., and Thompson, W.D. (1996). Methods in Observational Epidemiology, Oxford University Press Inc.. [2nd ed.]. Tables 12\u201315 Fleiss, Statistical Methods for Rates and Proportions, Formulas 3.18 & 3.19."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chia, L.W., Nguyen, T.V.H., Phan, V.N., Luu, T.T.N., Nguyen, G.K., Tan, S.Y., Rajindrajith, S., and Benninga, M.A. (2022). Prevalence and Risk Factors of Functional Gastrointestinal Disorders in Vietnamese Infants and Young Children. BMC Pediatr., 22.","DOI":"10.1186\/s12887-022-03378-z"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1053\/j.gastro.2016.02.016","article-title":"Childhood Functional Gastrointestinal Disorders: Neonate\/Toddler","volume":"150","author":"Benninga","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1097\/MPG.0000000000003653","article-title":"Prevalence and Risk Factors of Functional Gastrointestinal Disorders: A Cross-Sectional Study in Italian Infants and Young Children","volume":"76","author":"Scarpato","year":"2023","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Natividad, J.M., Marsaux, B., Rodenas, C.L.G., Rytz, A., Vandevijver, G., Marzorati, M., Van den Abbeele, P., Calatayud, M., and Rochat, F. (2022). Human Milk Oligosaccharides and Lactose Differentially Affect Infant Gut Microbiota and Intestinal Barrier In Vitro. Nutrients, 14.","DOI":"10.3390\/nu14122546"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ferrier, L., Eutam\u00e8ne, H., Siegwald, L., Marquard, A.M., Tondereau, V., Chevalier, J., Jacot, G.E., Favre, L., Theodorou, V., and Vicario, M. (2022). Human Milk Oligosaccharides Alleviate Stress-Induced Visceral Hypersensitivity and Associated Microbiota Dysbiosis. J. Nutr. Biochem., 99.","DOI":"10.1016\/j.jnutbio.2021.108865"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jpeds.2016.04.008","article-title":"Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents","volume":"177","author":"Lewis","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.cgh.2017.11.005","article-title":"Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents in the Mediterranean Region of Europe","volume":"16","author":"Scarpato","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.dld.2023.05.013","article-title":"Prevalence of Functional Gastrointestinal Disorders in Italian Children Living in Different Regions: Analysis of the Difference and the Role of Diet","volume":"55","author":"Cenni","year":"2023","journal-title":"Dig. Liver Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.jcmgh.2021.05.019","article-title":"Early Life Antibiotics Influence In Vivo and In Vitro Mouse Intestinal Epithelium Maturation and Functioning","volume":"12","author":"Garcia","year":"2021","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Schokker, D., Zhang, J., Vastenhouw, S.A., Heilig, H.G.H.J., Smidt, H., Rebel, J.M.J., and Smits, M.A. (2015). Long-Lasting Effects of Early-Life Antibiotic Treatment and Routine Animal Handling on Gut Microbiota Composition and Immune System in Pigs. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116523"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/s41467-022-28525-z","article-title":"Effects of Early-Life Antibiotics on the Developing Infant Gut Microbiome and Resistome: A Randomized Trial","volume":"13","author":"Reyman","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jpeds.2019.04.061","article-title":"Neonatal Antibiotics and Prematurity Are Associated with an Increased Risk of Functional Gastrointestinal Disorders in the First Year of Life","volume":"212","author":"Salvatore","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chanpong, A., Borrelli, O., and Thapar, N. (2023). The Potential Role of Microorganisms on Enteric Nervous System Development and Disease. Biomolecules, 13.","DOI":"10.3390\/biom13030447"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"G541","DOI":"10.1152\/ajpgi.00288.2020","article-title":"Early Life Interaction between the Microbiota and the Enteric Nervous System","volume":"319","author":"Foong","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1136\/gutjnl-2020-323020","article-title":"Gut Microbiota Composition Reflects Disease Severity and Dysfunctional Immune Responses in Patients with COVID-19","volume":"70","author":"Yeoh","year":"2021","journal-title":"Gut"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00734-20","DOI":"10.1128\/IAI.00734-20","article-title":"Influenza Virus Infection Impairs the Gut\u2019s Barrier Properties and Favors Secondary Enteric Bacterial Infection through Reduced Production of Short-Chain Fatty Acids","volume":"89","author":"Sencio","year":"2021","journal-title":"Infect. Immun."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/11\/1430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T08:30:32Z","timestamp":1761208232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/11\/1430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["children12111430"],"URL":"https:\/\/doi.org\/10.3390\/children12111430","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}