{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:50:28Z","timestamp":1790617828512,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2016YFC1305302"],"award-info":[{"award-number":["2016YFC1305302"]}]},{"name":"Clinical special project of integrated traditional Chinese and Western medicine in 2019"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Pediatr"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The real-world exposure levels of non-therapeutic antibiotics and neonicotinoids in type 1 diabetes (T1D) children and their associations as environmental triggers through gut microbiota shifts remained unknown. We thus investigated the antibiotics and neonicotinoids\u2019 exposure levels and their associations with gut microbiota in pediatric T1D.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Fifty-one newly onset T1D children along with 67 age-matched healthy controls were recruited. Urine concentrations of 28 antibiotics and 12 neonicotinoids were measured by mass spectrometry. Children were grouped according to the kinds of antibiotics\u2019 and neonicotinoids\u2019 exposures, respectively. The 16S rRNA of fecal gut microbiota was sequenced, and the correlation with urine antibiotics and neonicotinoids\u2019 concentrations was analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The overall detection rates of antibiotics were 72.5% and 61.2% among T1D and healthy children, whereas the neonicotinoids detection rates were 70.6% and 52.2% (<jats:italic>P<\/jats:italic>\u2009=\u20090.044). Children exposed to one kind of antibiotic or two or more kinds of neonicotinoids had higher risk of T1D, with the odd ratios of 2.579 and 3.911. Furthermore, co-exposure to antibiotics and neonicotinoids was associated with T1D, with the odd ratio of 4.924. Antibiotics or neonicotinoids exposure did not affect overall richness and diversity of gut microbiota. However, children who were exposed to neither antibiotics nor neonicotinoids had higher abundance of Lachnospiraceae than children who were exposed to antibiotics and neonicotinoids alone or together.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>High antibiotics and neonicotinoids exposures were found in T1D children, and they were associated with changes in gut microbiota featured with lower abundance of butyrate-producing genera, which might increase the risk of T1D.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12519-022-00589-3","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T03:21:51Z","timestamp":1659064911000},"page":"671-679","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Association between new onset type 1 diabetes and real-world antibiotics and neonicotinoids\u2019 exposure-related gut microbiota perturbation"],"prefix":"10.1007","volume":"18","author":[{"given":"Zhen-Ran","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xiao","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Yan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Qi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Wei","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Juan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Hong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"589_CR1","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1016\/S0140-6736(18)31320-5","volume":"391","author":"LA DiMeglio","year":"2018","unstructured":"DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet. 2018;391:2449\u201362.","journal-title":"Lancet"},{"key":"589_CR2","doi-asserted-by":"crossref","unstructured":"Anderson K, Norman D, Wittwer G. IDF DIABETES ATLAS Ninth edition. 2019. https:\/\/diabetesatlas.org\/. Accessed 27 Dec 2019","DOI":"10.1142\/9789811202094_0002"},{"key":"589_CR3","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1007\/s00592-014-0590-2","volume":"51","author":"Z Zhao","year":"2014","unstructured":"Zhao Z, Sun C, Wang C, Li P, Wang W, Ye J, et al. Rapidly rising incidence of childhood type 1 diabetes in Chinese population: epidemiology in Shanghai during 1997\u20132011. Acta Diabetol. 2014;51:947\u201353.","journal-title":"Acta Diabetol"},{"key":"589_CR4","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s41574-019-0254-y","volume":"15","author":"J Ilonen","year":"2019","unstructured":"Ilonen J, Lempainen J, Veijola R. The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat Rev Endocrinol. 2019;15:635\u201350.","journal-title":"Nat Rev Endocrinol"},{"key":"589_CR5","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1007\/s00125-018-4763-3","volume":"62","author":"CC Patterson","year":"2019","unstructured":"Patterson CC, Harjutsalo V, Rosenbauer J, Neu A, Cinek O, Skrivarhaug T, et al. Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989\u20132013: a multicentre prospective registration study. Diabetologia. 2019;62:408\u201317.","journal-title":"Diabetologia"},{"key":"589_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3043","volume":"34","author":"P Zheng","year":"2018","unstructured":"Zheng P, Li Z, Zhou Z. Gut microbiome in type 1 diabetes: a comprehensive review. Diabetes Metab Res Rev. 2018;34:e3043.","journal-title":"Diabetes Metab Res Rev"},{"key":"589_CR7","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1016\/j.celrep.2015.02.049","volume":"10","author":"JA Thompson","year":"2015","unstructured":"Thompson JA, Oliveira RA, Djukovic A, Ubeda C, Xavier KB. Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota. Cell Rep. 2015;10:1861\u201371.","journal-title":"Cell Rep"},{"key":"589_CR8","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1001\/jamapediatrics.2014.1539","volume":"168","author":"LC Bailey","year":"2014","unstructured":"Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr. 2014;168:1063\u20139.","journal-title":"JAMA Pediatr"},{"key":"589_CR9","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1136\/gut.2010.219683","volume":"60","author":"A Hviid","year":"2011","unstructured":"Hviid A, Svanstr\u00f6m H, Frisch M. Antibiotic use and inflammatory bowel diseases in childhood. Gut. 2011;60:49\u201354.","journal-title":"Gut"},{"key":"589_CR10","doi-asserted-by":"publisher","first-page":"16140","DOI":"10.1038\/nmicrobiol.2016.140","volume":"1","author":"AE Livanos","year":"2016","unstructured":"Livanos AE, Greiner TU, Vangay P, Pathmasiri W, Stewart D, McRitchie S, et al. Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice. Nat Microbiol. 2016;1:16140.","journal-title":"Nat Microbiol"},{"key":"589_CR11","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/s41564-018-0257-9","volume":"3","author":"A Palleja","year":"2018","unstructured":"Palleja A, Mikkelsen KH, Forslund SK, Kashani A, Allin KH, Nielsen T, et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol. 2018;3:1255\u201365.","journal-title":"Nat Microbiol"},{"key":"589_CR12","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1289\/EHP515","volume":"125","author":"AM Cimino","year":"2017","unstructured":"Cimino AM, Boyles AL, Thayer KA, Perry MJ. Effects of neonicotinoid pesticide exposure on human health: a systematic review. Environ Health Perspect. 2017;125:155\u201362.","journal-title":"Environ Health Perspect"},{"key":"589_CR13","doi-asserted-by":"publisher","first-page":"115290","DOI":"10.1016\/j.envpol.2020.115290","volume":"266","author":"G Yang","year":"2020","unstructured":"Yang G, Yuan X, Jin C, Wang D, Wang Y, Miao W, et al. Imidacloprid disturbed the gut barrier function and interfered with bile acids metabolism in mice. Environ Pollut. 2020;266:115290.","journal-title":"Environ Pollut."},{"key":"589_CR14","doi-asserted-by":"publisher","first-page":"116306","DOI":"10.1016\/j.envpol.2020.116306","volume":"271","author":"S Yan","year":"2021","unstructured":"Yan S, Tian S, Meng Z, Teng M, Sun W, Jia M, et al. Exposure to nitenpyram during pregnancy causes colonic mucosal damage and non-alcoholic steatohepatitis in mouse offspring: the role of gut microbiota. Environ Pollut. 2021;271:116306.","journal-title":"Environ Pollut."},{"key":"589_CR15","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/pedi.12773","volume":"19","author":"EJ Mayer-Davis","year":"2018","unstructured":"Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, et al. ISPAD Clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2018;19:7\u201319.","journal-title":"Pediatr Diabetes"},{"key":"589_CR16","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/nbt.2170","volume":"30","author":"D Reyon","year":"2012","unstructured":"Reyon D, Tsai SQ, Khgayter C, Foden JA, Sander JD, Joung JK. FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol. 2012;30:460\u20135.","journal-title":"Nat Biotechnol"},{"key":"589_CR17","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","volume":"7","author":"JG Caporaso","year":"2010","unstructured":"Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high- throughput community sequencing data. Nat Methods. 2010;7:335\u20136.","journal-title":"Nat Methods"},{"key":"589_CR18","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1093\/bioinformatics\/btr381","volume":"27","author":"RC Edgar","year":"2011","unstructured":"Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27:2194\u2013200.","journal-title":"Bioinformatics"},{"key":"589_CR19","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","volume":"73","author":"Q Wang","year":"2007","unstructured":"Wang Q, Garrity GM, Tiedje JM, Cole JR. Na\u00efve Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73:5261\u20137.","journal-title":"Appl Environ Microbiol"},{"key":"589_CR20","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.envint.2018.09.032","volume":"12","author":"H Wang","year":"2018","unstructured":"Wang H, Tang C, Yang J, Wang N, Jiang F, Xia Q, et al. Predictors of urinary antibiotics in children of Shanghai and health risk assessment. Environ Int. 2018;12:507\u201314.","journal-title":"Environ Int"},{"key":"589_CR21","doi-asserted-by":"publisher","first-page":"105918","DOI":"10.1016\/j.envint.2020.105918","volume":"143","author":"H Wang","year":"2020","unstructured":"Wang H, Yang D, Fang H, Han M, Tang C, Wu J, et al. Predictors, sources, and health risk of exposure to neonicotinoids in Chinese school children: a biomonitoring-based study. Environ Int. 2020;143:105918.","journal-title":"Environ Int."},{"key":"589_CR22","doi-asserted-by":"publisher","first-page":"7569","DOI":"10.1021\/acs.jafc.9b01334","volume":"67","author":"J Chen","year":"2019","unstructured":"Chen J, Ying GG, Deng WJ. Antibiotic residues in food: extraction, analysis, and human health concerns. J Agric Food Chem. 2019;67:7569\u201386.","journal-title":"J Agric Food Chem"},{"key":"589_CR23","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.envint.2017.08.014","volume":"108","author":"N Li","year":"2017","unstructured":"Li N, Ho KWK, Ying GG, Deng WJ. Veterinary antibiotics in food, drinking water, and the urine of preschool children in Hong Kong. Environ Int. 2017;108:246\u201352.","journal-title":"Environ Int"},{"key":"589_CR24","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.scitotenv.2019.04.267","volume":"675","author":"Y Wan","year":"2019","unstructured":"Wan Y, Wang Y, Xia W, He Z, Xu S. Neonicotinoids in raw, finished, and tap water from Wuhan, Central China: assessment of human exposure potential. Sci Total Environ. 2019;675:513\u20139.","journal-title":"Sci Total Environ"},{"key":"589_CR25","doi-asserted-by":"publisher","first-page":"133790","DOI":"10.1016\/j.scitotenv.2019.133790","volume":"695","author":"A Wang","year":"2019","unstructured":"Wang A, Mahai G, Wan Y, Jiang Y, Meng Q, Xia W, et al. Neonicotinoids and carbendazim in indoor dust from three cities in China: spatial and temporal variations. Sci Total Environ. 2019;695:133790.","journal-title":"Sci Total Environ."},{"key":"589_CR26","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.chemosphere.2018.09.152","volume":"215","author":"R Wei","year":"2019","unstructured":"Wei R, He T, Zhang S, Zhu L, Shang B, Li Z, et al. Occurrence of seventeen veterinary antibiotics and resistant bacterias in manure-fertilized vegetable farm soil in four provinces of China. Chemosphere. 2019;215:234\u201340.","journal-title":"Chemosphere"},{"key":"589_CR27","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.envres.2016.01.028","volume":"147","author":"A Osaka","year":"2016","unstructured":"Osaka A, Ueyama J, Kondo T, Nomura H, Sugiura Y, Saito I, et al. Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids. Environ Res. 2016;147:89\u201396.","journal-title":"Environ Res"},{"key":"589_CR28","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1093\/cid\/cit439","volume":"57","author":"H Chou","year":"2013","unstructured":"Chou H, Wang J, Chang C, Lee J, Shau W, Lai M. Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan. Clin Infect Dis. 2013;57:971\u201380.","journal-title":"Clin Infect Dis"},{"key":"589_CR29","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.envres.2014.08.030","volume":"135","author":"SL Carmichael","year":"2014","unstructured":"Carmichael SL, Yang W, Roberts E, Kegley SE, Padula AM, English PB, et al. Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California. Environ Res. 2014;135:133\u20138.","journal-title":"Environ Res"},{"key":"589_CR30","first-page":"1","volume":"13","author":"AP Keil","year":"2014","unstructured":"Keil AP, Daniels JL, Hertz-Picciotto I. Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Environ Heal A Glob Access Sci Source. 2014;13:1\u201310.","journal-title":"Environ Heal A Glob Access Sci Source"},{"key":"589_CR31","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1097\/JU.0000000000001227","volume":"204","author":"Y Akagawa","year":"2020","unstructured":"Akagawa Y, Kimata T, Akagawa S, Yamaguchi T, Kato S, Yamanouchi S, et al. Impact of long-term low dose antibiotic prophylaxis on Gut microbiota in children. J Urol. 2020;204:1320\u20135.","journal-title":"J Urol"},{"key":"589_CR32","doi-asserted-by":"publisher","first-page":"104989","DOI":"10.1016\/j.envint.2019.104989","volume":"131","author":"TP Keerthisinghe","year":"2019","unstructured":"Keerthisinghe TP, Wang M, Zhang Y, Dong W, Fang M. Low-dose tetracycline exposure alters gut bacterial metabolism and host-immune response: \u201cpersonalized\u201d effect? Environ Int. 2019;131:104989.","journal-title":"Environ Int."},{"key":"589_CR33","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/nrendo.2015.218","volume":"12","author":"M Knip","year":"2016","unstructured":"Knip M, Siljander H. The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol. 2016;12:154\u201367.","journal-title":"Nat Rev Endocrinol"},{"key":"589_CR34","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41586-018-0620-2","volume":"562","author":"T Vatanen","year":"2018","unstructured":"Vatanen T, Franzosa EA, Schwager R, Tripathi S, Arthur TD, Vehik K, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018;562:589\u201394.","journal-title":"Nature"},{"key":"589_CR35","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1159\/000492853","volume":"49","author":"Y Feng","year":"2018","unstructured":"Feng Y, Wang Y, Wang P, Huang Y, Wang F. Short-Chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of NLRP3 inflammasome and autophagy. Cell Physiol Biochem. 2018;49:190\u2013205.","journal-title":"Cell Physiol Biochem"}],"container-title":["World Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12519-022-00589-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12519-022-00589-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12519-022-00589-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T11:32:58Z","timestamp":1663587178000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12519-022-00589-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["589"],"URL":"https:\/\/doi.org\/10.1007\/s12519-022-00589-3","relation":{},"ISSN":["1708-8569","1867-0687"],"issn-type":[{"value":"1708-8569","type":"print"},{"value":"1867-0687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,29]]},"assertion":[{"value":"18 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflict of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the Ethics Committee of Children\u2019s Hospital of Fudan University ([2019]210). The guardians of the children provided written informed consent before information and sample collection.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}