{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:23:31Z","timestamp":1792027411309,"version":"4.4.0"},"reference-count":74,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["#DP130101596"],"award-info":[{"award-number":["#DP130101596"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30\u2010DK56338"],"award-info":[{"award-number":["P30\u2010DK56338"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK130517"],"award-info":[{"award-number":["R01DK130517"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01\u2010AI24290"],"award-info":[{"award-number":["U01\u2010AI24290"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01\u2010AI152999"],"award-info":[{"award-number":["P01\u2010AI152999"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000056","name":"National Institute of Nursing Research","doi-asserted-by":"publisher","award":["R01\u2010NR013497"],"award-info":[{"award-number":["R01\u2010NR013497"]}],"id":[{"id":"10.13039\/100000056","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Infants and young children receive the highest exposures to antibiotics globally. Although there is building evidence that early life exposure to antibiotics increases susceptibility to various diseases including gut disorders later in life, the lasting impact of early life antibiotics on the physiology of the gut and its enteric nervous system (ENS) remains unclear. We treated neonatal mice with the antibiotic vancomycin during their first 10 postnatal days, then examined potential lasting effects of the antibiotic treatment on their colons during young adulthood (6\u00a0weeks old). We found that neonatal vancomycin treatment disrupted the gut functions of young adult female and male mice differently. Antibiotic\u2010exposed females had significantly longer whole gut transit while antibiotic\u2010treated males had significantly lower faecal weights compared to controls. Both male and female antibiotic\u2010treated mice had greater percentages of faecal water content. Neonatal vancomycin treatment also had sexually dimorphic impacts on the neurochemistry and Ca<jats:sup>2+<\/jats:sup> activity of young adult myenteric and submucosal neurons. Myenteric neurons of male mice were more disrupted than those of females, while opposing changes in submucosal neurons were seen in each sex. Neonatal vancomycin also induced sustained changes in colonic microbiota and lasting depletion of mucosal serotonin (5\u2010HT) levels. Antibiotic impacts on microbiota and mucosal 5\u2010HT were not sex\u2010dependent, but we propose that the responses of the host to these changes are sex\u2010specific. This first demonstration of long\u2010term impacts of neonatal antibiotics on the ENS, gut microbiota and mucosal 5\u2010HT has important implications for gut function and other physiological systems of the host.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15201-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Early life exposure to antibiotics can increase susceptibility to diseases including functional gastrointestinal (GI) disorders later in life. Yet, the lasting impact of this common therapy on the gut and its enteric nervous system (ENS) remains unclear.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We investigated the long\u2010term impact of neonatal antibiotic treatment by treating mice with the antibiotic vancomycin during their neonatal period, then examining their colons during young adulthood.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Adolescent female mice given neonatal vancomycin treatment had significantly longer whole gut transit times, while adolescent male and female mice treated with neonatal antibiotics had significantly wetter stools.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Effects of neonatal vancomycin treatment on the neurochemistry and Ca<jats:sup>2+<\/jats:sup> activity of myenteric and submucosal neurons were sexually dimorphic. Neonatal vancomycin also had lasting effects on the colonic microbiome and mucosal serotonin biosynthesis that were not sex\u2010dependent.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Different male and female responses to antibiotic\u2010induced disruptions of the ENS, microbiota and mucosal serotonin biosynthesis can lead to sex\u2010specific impacts on gut function.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp282939","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T19:23:39Z","timestamp":1662751419000},"page":"4303-4323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Neonatal antibiotics have long term sex\u2010dependent effects on the enteric nervous system"],"prefix":"10.1113","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8370-3179","authenticated-orcid":false,"given":"Sabrina S. B.","family":"Poon","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin Y.","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine  Houston TX USA"},{"name":"Texas Children's Microbiome Center Texas Children's Hospital  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavitha","family":"Parathan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazli","family":"Yalcinkaya","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine  Houston TX USA"},{"name":"Texas Children's Microbiome Center Texas Children's Hospital  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Haag","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine  Houston TX USA"},{"name":"Texas Children's Microbiome Center Texas Children's Hospital  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Ann","family":"Luna","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine  Houston TX USA"},{"name":"Texas Children's Microbiome Center Texas Children's Hospital  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-7717","authenticated-orcid":false,"given":"Joel C.","family":"Bornstein","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor C.","family":"Savidge","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine  Houston TX USA"},{"name":"Texas Children's Microbiome Center Texas Children's Hospital  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-5520","authenticated-orcid":false,"given":"Jaime P. P.","family":"Foong","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272071"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.647555"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23423"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1986.sp016339"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-809954-4.00019-0"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2014.103"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-16-06348.2001"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.05.052"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(07)00562-3"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.396"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.003"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.025"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-27592-5_13"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.21.001.2009"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4175-14.2015"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.225938"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.265686"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00288.2020"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1028-z"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00118"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.32"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2003.12.004"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-1105-4"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32835bc703"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-022-03120-9"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270818"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015907780077141"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.09.071"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2564-7"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00436"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.256230"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123436"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.04.009"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00088.2020"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00136-2"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.06.017"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-017-0267-5"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00097"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619406114"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-016-0294-z"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58200"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam7511"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.42914"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11020234"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2016.11.008"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.09.032"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410000303"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00391"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-009-0773-2"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00736-x"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2014.00109"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.08.016"},{"key":"e_1_2_5_54_1","first-page":"489","article-title":"Antibiotics in early life: Dysbiosis and the damage done","volume":"42","author":"Neuman H.","year":"2018","journal-title":"FEMS Microbiology Review"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2019.10.011"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903140411"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-020-00688-1"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-008-0684-7"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-259598"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.185421"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00444.2006"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijpvm.IJPVM_328_17"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050565"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199806)251:2<185::AID-AR6>3.0.CO;2-Y"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.398"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1136\/fn.79.2.F105"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.684096"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.01.035"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00426"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1398"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1239-15.2015"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2020.12.014"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2012.00041"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.047"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.021"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP282939","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP282939","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP282939","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP282939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T07:26:56Z","timestamp":1692689216000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP282939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":74,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1113\/JP282939"],"URL":"https:\/\/doi.org\/10.1113\/jp282939","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]},"assertion":[{"value":"2022-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}