{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:31:52Z","timestamp":1790767912771,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JGH Open"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This case\u2013control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at\u2010risk individuals including non\u2010affected first\u2010degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self\u2010developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98\u2009\u00b1\u200913.76\u2009years; 58.3% male), 73 FDR (mean age: 49.35\u2009\u00b1\u200913.28\u2009years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50\u2009\u00b1\u200913.25\u2009years; 47.5% male), and 78 HC (mean age: 45.57\u2009\u00b1\u200911.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18\u2009years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38\u20138.69;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use &lt;18\u2009years old was a risk factor for CD development in the Chinese (adjusted OR 4.80, 95% CI 1.62\u201312.24;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.005) but not in Australian populations (OR 1.80, 95% CI 0.33\u20139.95;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.498).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Use of antibiotics &lt;18\u2009years was a risk factor for CD development. Attention should be paid to identifying modifiable environmental risk factors in early childhood, especially in at\u2010risk families.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgh3.12755","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T07:44:38Z","timestamp":1654069478000},"page":"369-377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Childhood antibiotics as a risk factor for Crohn's disease: The\n                    <scp>ENIGMA<\/scp>\n                    International Cohort Study"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5221-7349","authenticated-orcid":false,"given":"Joyce W Y","family":"Mak","sequence":"first","affiliation":[{"name":"Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology First Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalise","family":"Stanley","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Lin","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Morrison","sequence":"additional","affiliation":[{"name":"Diamantina Institute, Faculty of Medicine The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Y L","family":"Ching","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junkun","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology First Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L","family":"Wilson\u2010O'Brien","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Feng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"},{"name":"LKS Institute of Health Sciences, State Key Laboratory of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"},{"name":"Microbiota I\u2010Center (MagIC)  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1627-2057","authenticated-orcid":false,"given":"Amy L","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Or","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"},{"name":"LKS Institute of Health Sciences, State Key Laboratory of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-0899","authenticated-orcid":false,"given":"Gina L","family":"Trakman","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie Y Y","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"},{"name":"Microbiota I\u2010Center (MagIC)  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J Y","family":"Sung","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Hu","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinglei","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology First Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-7199","authenticated-orcid":false,"given":"Michael A","family":"Kamm","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew C","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"},{"name":"LKS Institute of Health Sciences, State Key Laboratory of Digestive Disease The Chinese University of Hong Kong  Shatin Hong Kong"},{"name":"Microbiota I\u2010Center (MagIC)  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32448-0"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307410"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303661"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000846"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3760"},{"key":"e_1_2_5_7_1","first-page":"339","article-title":"Environmental risk factors for inflammatory bowel disease","volume":"6","author":"Molodecky NA","year":"2010","journal-title":"Gastroenterol. 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