Intrapartum antibiotic prophylaxis (IAP) is commonly used during C-section delivery and in Group B Streptococcus-positive women before vaginal delivery. Here, we primarily aimed to investigate the effect of IAP on the neonatal oral and fecal bacteriomes in the first week of life. In this preliminary study, maternal and neonatal oral swabs and neonatal fecal (meconium and transitional stool) swabs were selected from a pool of samples from healthy mother-neonate pairs participating in the pilot phase of CELSPAC: TNG during their hospital stay. The DNA was extracted and bacteriome profiles were determined by 16S rRNA amplicon sequencing (Illumina). In the final dataset, 33 mother-neonate pairs were exposed to antibiotics during C-section or vaginal delivery (cases; +IAP) and the vaginal delivery without IAP (controls, -IAP) took place in 33 mother-neonate pairs. Differences in alpha diversity (Shannon index, p=0.01) and bacterial composition (PERMANOVA, p<0.05) between the +IAP and -IAP groups were detected only in neonatal oral samples collected ≤48 h after birth. No significant differences between meconium bacteriomes of the +IAP and -IAP groups were observed (p>0.05). However, the IAP was associated with decreased alpha diversity (number of amplicon sequence variants, p<0.001), decreased relative abundances of the genera Bacteroides and Bifidobacterium, and increased relative abundances of genera Enterococcus and Rothia (q<0.01 for all of them) in transitional stool samples. The findings of this study suggest that exposure to IAP may significantly influence the early development of the neonatal oral and gut microbiomes. IAP affected the neonatal oral bacteriome in the first two days after birth as well as the neonatal fecal bacteriome in transitional stool samples. In addition, it highlights the necessity for further investigation into the potential long-term health impacts on children.

BioVendor MDx Karasek 1 Brno Czech Republic

Clinic of Maxillofacial Surgery University Hospital Brno Jihlavska 20 Brno Czech Republic

Department of Gynecology and Obstetrics Faculty of Medicine Masaryk University Kamenice 5 Brno Czech Republic

Department of Gynecology and Obstetrics University Hospital Brno Jihlavska 20 Brno Czech Republic

Department of Neonatology Faculty of Medicine Masaryk University Kamenice 5 Brno Czech Republic

Department of Neonatology University Hospital Brno Jihlavska 20 Brno Czech Republic

RECETOX Faculty of Science Masaryk University Kotlarska 2 Brno Czech Republic

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Shao, Y. et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature.574, 117–21 (2019). PubMed PMC

Mueller, N. T., Bakacs, E., Combellick, J., Grigoryan, Z. & Dominguez-Bello, M. G. The infant microbiome development: Mom matters. Trends Mol. Med.21, 109–17 (2015). PubMed PMC

Grech, A. et al. Maternal exposures and the infant gut microbiome: A systematic review with meta-analysis. Gut Microbes13, 1–30 (2021). PubMed PMC

Bäckhed, F. et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe17, 690–703 (2015). PubMed

Rutayisire, E., Huang, K., Liu, Y. & Tao, F. The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants’ life: A systematic review. BMC Gastroenterol.16, 86 (2016). PubMed PMC

Shaterian, N., Abdi, F., Ghavidel, N. & Alidost, F. Role of cesarean section in the development of neonatal gut microbiota: A systematic review. Open Med. Wars Pol.16, 624–39 (2021). PubMed PMC

Pivrncova, E., Kotaskova, I. & Thon, V. Neonatal diet and gut microbiome development after C-section during the first three months after birth: A systematic review. Front. Nutr.9, 941549 (2022). PubMed PMC

Nardi, G. M. et al. Maternal and neonatal oral microbiome developmental patterns and correlated factors: A systematic review—does the apple fall close to the tree?. Int. J. Environ. Res. Public Health18, 5569 (2021). PubMed PMC

Sandall, J. et al. Short-term and long-term effects of caesarean section on the health of women and children. Lancet (London, England)392, 1349–57 (2018). PubMed

Dominguez-Bello, M. G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. U. S. A.107, 11971–5 (2010). PubMed PMC

Bokulich, N. A. et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci. Transl. Med.10.1126/scitranslmed.aad7121 (2016). PubMed PMC

Nogacka, A. et al. Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates. Microbiome5, 93 (2017). PubMed PMC

Money, D., Allen, V. M., Infectious Diseases Committee. The prevention of early-onset neonatal group B streptococcal disease. J. Obstet. Gynaecol. Can. JOGC35, 939–948 (2013). PubMed

Betran, A. P., Ye, J., Moller, A.-B., Souza, J. P. & Zhang, J. Trends and projections of caesarean section rates: Global and regional estimates. BMJ Glob. Health6, e005671 (2021). PubMed PMC

Seale, A. C. et al. Estimates of the burden of group b streptococcal disease worldwide for pregnant women, stillbirths, and children. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am.65(Suppl 2), S200-19 (2017). PubMed PMC

Trijbels-Smeulders, M. et al. Epidemiology of neonatal group B streptococcal disease in the Netherlands before and after introduction of guidelines for prevention. Arch. Dis. Child. Fetal Neonatal Ed.92, F271-276 (2007). PubMed PMC

Schrag, S. J. & Verani, J. R. Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: Experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine31(Suppl 4), D20-26 (2013). PubMed PMC

Zhu, Y. & Lin, X.-Z. Updates in prevention policies of early-onset group B streptococcal infection in newborns. Pediatr. Neonatol.62, 465–75 (2021). PubMed

Hasperhoven, G., Al-Nasiry, S., Bekker, V., Villamor, E. & Kramer, B. Universal screening versus risk-based protocols for antibiotic prophylaxis during childbirth to prevent early-onset group B streptococcal disease: A systematic review and meta-analysis. BJOG Int. J. Obstet. Gynaecol.127, 680–91 (2020). PubMed PMC

Van Dyke, M. K. et al. Evaluation of universal antenatal screening for group B streptococcus. N. Engl. J. Med.360, 2626–36 (2009). PubMed

Stearns, J. C. et al. Intrapartum antibiotics for GBS prophylaxis alter colonization patterns in the early infant gut microbiome of low risk infants. Sci. Rep.7, 16527 (2017). PubMed PMC

Zimmermann, P. & Curtis, N. Effect of intrapartum antibiotics on the intestinal microbiota of infants: A systematic review. Arch. Dis. Child. Fetal Neonatal Ed.105, 201–8 (2020). PubMed

Hirsch, A. G. et al. Early life antibiotic use and subsequent diagnosis of food allergy and allergic diseases. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol.47, 236–44 (2017). PubMed PMC

Kummeling, I. et al. Early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in the first 2 years of life: The KOALA birth cohort study. Pediatrics119, e225-31 (2007). PubMed

Azad, M. B., Bridgman, S. L., Becker, A. B. & Kozyrskyj, A. L. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int. J. Obes.38, 1290–8 (2014). PubMed

Gomez Arango, L. et al. Antibiotic treatment at delivery shapes the initial oral microbiome in neonates. Sci. Rep.7, 43481 (2017). PubMed PMC

Tapiainen, T. et al. Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants. Sci. Rep.9, 10635 (2019). PubMed PMC

Chen, Y. Y. et al. Impact of maternal intrapartum antibiotics, and caesarean section with and without labour on bifidobacterium and other infant gut microbiota. Microorganisms9, 1847 (2021). PubMed PMC

Azad, M. et al. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: A prospective cohort study. BJOG Int. J. Obstet. Gynaecol.123, 983–93 (2016). PubMed

Aloisio, I. et al. Influence of intrapartum antibiotic prophylaxis against group B Streptococcus on the early newborn gut composition and evaluation of the anti-Streptococcus activity of Bifidobacterium strains. Appl. Microbiol. Biotechnol.98, 6051–60 (2014). PubMed

Zhou, P. et al. Perinatal antibiotic exposure affects the transmission between maternal and neonatal microbiota and is associated with early-onset sepsis. mSphere5, e00984-19 (2020). PubMed PMC

Pavlova, T. et al. Urinary intermediates of tryptophan as indicators of the gut microbial metabolism. Anal. Chim. Acta987, 72–80 (2017). PubMed

Videnska, P. et al. Stool sampling and DNA isolation kits affect DNA quality and bacterial composition following 16S rRNA gene sequencing using MiSeq Illumina platform. Sci. Rep.9, 13837 (2019). PubMed PMC

Douglas, C. A. et al. DNA extraction approaches substantially influence the assessment of the human breast milk microbiome. Sci. Rep.10, 123 (2020). PubMed PMC

Claassen, S. et al. A comparison of the efficiency of five different commercial DNA extraction kits for extraction of DNA from faecal samples. J. Microbiol. Methods94, 103–10 (2013). PubMed PMC

Kotásková, I. et al. Actinotignum schaalii: Relation to concomitants and connection to patients’ conditions in polymicrobial biofilms of urinary tract catheters and urines. Microorganisms9, 669 (2021). PubMed PMC

Tourlousse, D. M. et al. Synthetic spike-in standards for high-throughput 16S rRNA gene amplicon sequencing. Nucleic Acids Res.45, e23 (2017). PubMed PMC

Caporaso, J. G. et al. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc. Natl. Acad. Sci.108, 4516–22 (2011). PubMed PMC

Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods13, 581–3 (2016). PubMed PMC

Aronesty, E. Comparison of sequencing utility programs. Open Bioinform. J.7, 1–8 (2013).

Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods7, 335–6 (2010). PubMed PMC

Quast, C. et al. The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools. Nucleic Acids Res.41, D590-6 (2013). PubMed PMC

Baldassarre, M. E. et al. Duration of meconium passage in preterm and term infants. Arch. Dis. Child. Fetal Neonatal Ed.95, F74-75 (2010). PubMed

Davis, N. M., Proctor, D. M., Holmes, S. P., Relman, D. A. & Callahan, B. J. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome6, 226 (2018). PubMed PMC

Pincus, R. & Aitchison, J. The Statistical Analysis of Compositional Data. Biom J.30, 794–794 (Chapman and Hall, London, New York, 1988).

R: The R Project for Statistical Computing. https://www.r-project.org/ (2023).

Van den Boogaart, K. & Tolosana-Delgado, R. Compositional data analysis with `R’ and the package ‘compositions’. Geol. Soc.264(1), 119–127 (2006).

Oksanen, J, et al. Vegan: Community Ecology Package. http://cran.r-project.org (2022).

Kassambara, A. & Mundt, F. Factoextra: Extract and visualize the results of multivariate data analyses. https://CRAN.R-project.org/package=factoextra (2020).

Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2009).

Murray, M. & Blume, J. FDRestimation: Estimate, Plot, and Summarize False Discovery Rates. 10.12688/f1000research.52999.2 (2022).

Conway, J. & Gehlenborg N. UpSetR: A More Scalable Alternative to Venn and Euler Diagrams for Visualizing Intersecting Sets. 10.1093/bioinformatics/btx364 (2019).

Guo, H. et al. The dynamic communities of oral microbiome in neonates. Front. Microbiol.13, 1052525 (2022). PubMed PMC

Ferretti, P. et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe24, 133-145.e5 (2018). PubMed PMC

Dzidic, M. et al. Oral microbiome development during childhood: An ecological succession influenced by postnatal factors and associated with tooth decay. ISME J.12, 2292–306 (2018). PubMed PMC

Belizário, J. E. & Napolitano, M. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front. Microbiol.6, 1050 (2015). PubMed PMC

Xiao, J., Fiscella, K. A. & Gill, S. R. Oral microbiome: Possible harbinger for children’s health. Int. J. Oral Sci.12, 1–13 (2020). PubMed PMC

Sampaio-Maia, B. & Monteiro-Silva, F. Acquisition and maturation of oral microbiome throughout childhood: An update. Dent. Res. J.11, 291–301 (2014). PubMed PMC

Chu, D. M. et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat. Med.23, 314–26 (2017). PubMed PMC

Verma, D., Garg, P. K. & Dubey, A. K. Insights into the human oral microbiome. Arch. Microbiol.200, 525–40 (2018). PubMed

Lif Holgerson, P., Harnevik, L., Hernell, O., Tanner, A. C. R. & Johansson, I. Mode of birth delivery affects oral microbiota in infants. J. Dent. Res.90, 1183–8 (2011). PubMed PMC

Dzidic, M. et al. Oral microbiota maturation during the first 7 years of life in relation to allergy development. Allergy73, 2000–11 (2018). PubMed

Boix-Amorós, A., Collado, M. C. & Mira, A. Relationship between milk microbiota, bacterial load, macronutrients, and human cells during lactation. Front. Microbiol.7, 492 (2016). PubMed PMC

Miyoshi, T. et al. Gemella haemolysans inhibits the growth of the periodontal pathogen Porphyromonas gingivalis. Sci. Rep.11, 11742 (2021). PubMed PMC

Peng, X. et al. Oral microbiota in human systematic diseases. Int. J. Oral Sci.14, 1–11 (2022). PubMed PMC

Li, H. et al. The impacts of delivery mode on infant’s oral microflora. Sci. Rep.8, 11938 (2018). PubMed PMC

Hurley, E. et al. The microbiota of the mother at birth and its influence on the emerging infant oral microbiota from birth to 1 year of age: A cohort study. J. Oral Microbiol.11, 1599652 (2019). PubMed PMC

Kennedy, B. et al. Oral microbiota development in early childhood. Sci. Rep.9, 19025 (2019). PubMed PMC

Dierikx, T. H. et al. The influence of prenatal and intrapartum antibiotics on intestinal microbiota colonisation in infants: A systematic review. J. Infect.81, 190–204 (2020). PubMed

Jauréguy, F. et al. Effects of intrapartum penicillin prophylaxis on intestinal bacterial colonization in infants. J. Clin. Microbiol.42, 5184–8 (2004). PubMed PMC

Arboleya, S., Saturio, S. & Gueimonde, M. Impact of intrapartum antibiotics on the developing microbiota: A review. Microbiome Res. Rep.1, 22 (2022). PubMed PMC

Imoto, N. et al. Administration of β-lactam antibiotics and delivery method correlate with intestinal abundances of Bifidobacteria and Bacteroides in early infancy, in Japan. Sci. Rep.11, 6231 (2021). PubMed PMC

Saturio, S. et al. Effect of intrapartum antibiotics prophylaxis on the bifidobacterial establishment within the neonatal gut. Microorganisms9, 1867 (2021). PubMed PMC

Corvaglia, L. et al. Influence of intrapartum antibiotic prophylaxis for group B streptococcus on gut microbiota in the first month of life. J. Pediatr. Gastroenterol. Nutr.62, 304 (2016). PubMed

Dierikx, T. et al. Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: A randomised controlled trial. Gut71, 1803–11 (2022). PubMed PMC

Mazzola, G. et al. Early gut microbiota perturbations following intrapartum antibiotic prophylaxis to prevent group B streptococcal disease. PLoS ONE11, e0157527 (2016). PubMed PMC