{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:49:15Z","timestamp":1790405355367,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"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. Microbiol."],"abstract":"<jats:p>Maternal antibiotic treatment (MAT) during prenatal and intrapartum periods alters the bacterial composition and diversity of the intestinal microbiota of the offspring. The effect of MAT during pregnancy on the intestinal microbiota and its relationship with intestinal development remain unknown. This study investigated the effects of MAT during pregnancy on intestinal microbiota, injury and inflammation, vascularization, cellular proliferation, and the intestinal barrier in neonatal mice. At timed intervals, we fed pregnant C57BL\/6N mice sterile drinking water containing antibiotics (ampicillin, gentamicin, and vancomycin; all 1 mg\/ml) from gestational day 15 to delivery. The control dams were fed sterile drinking water. Antibiotic administration was halted immediately after birth. On postnatal day 7, the intestinal microbiota was sampled from the lower gastrointestinal tract and the ileum was harvested for histology, Western blot, and cytokines analyses. MAT significantly reduced the relative abundance of <jats:italic>Bacteroidetes<\/jats:italic> and <jats:italic>Firmicutes<\/jats:italic> and significantly increased the relative abundance of <jats:italic>Proteobacteria<\/jats:italic> in the intestine compared with their abundances in the control group. MAT also significantly increased intestinal injury score and cytokine levels, reduced the number of intestinal goblet cells and proliferating cell nuclear antigen-positive cells, and reduced the expressions of vascular endothelial growth factor and tight junction proteins. Therefore, we proposed that maternal antibiotic exposure during pregnancy disrupts the intestinal microbiota and intestinal development in neonatal mice.<\/jats:p>","DOI":"10.3389\/fmicb.2021.684233","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T08:45:38Z","timestamp":1622796338000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Maternal Antibiotic Treatment Disrupts the Intestinal Microbiota and Intestinal Development in Neonatal Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Chung-Ming","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Chu","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen S. 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Pathol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jinf.2020.05.002","article-title":"The influence of prenatal and intrapartum antibiotics on intestinal microbiota colonisation in infants: a systematic review","volume":"81","author":"Dierikx","year":"2020","journal-title":"J. Infect."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"dmm040808","DOI":"10.1242\/dmm.040808","article-title":"Fetal exposure to maternal inflammation interrupts murine intestinal development and increases susceptibility to neonatal intestinal injury","volume":"12","author":"Elgin","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"3768","DOI":"10.4049\/jimmunol.1502322","article-title":"Maternal antibiotic treatment impacts development of the neonatal intestinal microbiome and antiviral immunity","volume":"196","author":"Gonzalez-Perez","year":"2016","journal-title":"J. Immunol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"eaaf9412","DOI":"10.1126\/scitranslmed.aaf9412","article-title":"Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection","volume":"9","author":"Gray","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.chom.2015.03.005","article-title":"Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function","volume":"17","author":"Kelly","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1702070","DOI":"10.1183\/13993003.02070-2017","article-title":"Prenatal antibiotic exposure and childhood asthma: a population-based study","volume":"52","author":"Loewen","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"S150","DOI":"10.1513\/AnnalsATS.201503-133AW","article-title":"The gut-lung axis in respiratory disease","volume":"12","author":"Marsland","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","article-title":"Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"McMurdie","year":"2013","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/ije\/dyx272","article-title":"Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort study","volume":"47","author":"Miller","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00404-010-1646-3","article-title":"Antibiotic chemotherapy during pregnancy and lactation period: aspects for consideration","volume":"283","author":"Mylonas","year":"2011","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"12974","DOI":"10.1038\/s41598-020-69797-z","article-title":"Transient neonatal antibiotic exposure increases susceptibility to late-onset sepsis driven by microbiota-dependent suppression of type 3 innate lymphoid cells","volume":"10","author":"Niu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.clim.2015.05.014","article-title":"Immune-microbiota interactions in health and disease","volume":"159","author":"Palm","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.jpeds.2018.01.056","article-title":"The impact of maternal antibiotics on neonatal disease","volume":"197","author":"Reed","year":"2018","journal-title":"J. Pediatr."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nature10893","article-title":"Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling","volume":"483","author":"Reinhardt","year":"2012","journal-title":"Nature"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1093\/bioinformatics\/btq706","article-title":"Phangorn: phylogenetic analysis in R","volume":"27","author":"Schliep","year":"2011","journal-title":"Bioinformatics"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s40168-020-00940-8","article-title":"Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function","volume":"8","author":"Selma-Royo","year":"2020","journal-title":"Microbiome"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"917","DOI":"10.5152\/tjg.2019.18681","article-title":"Determination of the changes on the small intestine of pregnant mice by histological, enzyme histochemical, and immunohistochemical methods","volume":"30","author":"\u015eensoy","year":"2019","journal-title":"Turk. J. Gastroenterol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nrmicro2974","article-title":"The gut microbiota-masters of host development and physiology","volume":"11","author":"Sommer","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/s42003-018-0140-5","article-title":"Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups","volume":"1","author":"Tulstrup","year":"2018","journal-title":"Commun. Biol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/ijo.2013.47","article-title":"Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring","volume":"37","author":"Vidal","year":"2013","journal-title":"Int. J. 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