Vertical Transmission of Gut Microbiome and Antimicrobial Resistance Genes in Infants Exposed to Antibiotics at Birth

Weizhong Li, Terhi Tapiainen, Lauren Brinkac, Hernan A Lorenzi, Kelvin Moncera, Mysore V Tejesvi, Jarmo Salo, Karen E Nelson, Weizhong Li, Terhi Tapiainen, Lauren Brinkac, Hernan A Lorenzi, Kelvin Moncera, Mysore V Tejesvi, Jarmo Salo, Karen E Nelson

Abstract

Vertical transmission of maternal microbes is a major route for establishing the gut microbiome in newborns. The impact of perinatal antibiotics on vertical transmission of microbes and antimicrobial resistance is not well understood. Using a metagenomic approach, we analyzed the fecal samples from mothers and vaginally delivered infants from a control group (10 pairs) and a treatment group (10 pairs) receiving perinatal antibiotics. Antibiotic-usage had a significant impact on the main source of inoculum in the gut microbiome of newborns. The control group had significantly more species transmitted from mothers to infants (P = .03) than the antibiotic-treated group. Approximately 72% of the gut microbial population of infants at 3-7 days after birth in the control group was transmitted from their mothers, versus only 25% in the antibiotic-treated group. In conclusion, perinatal antibiotics markedly disturbed vertical transmission and changed the source of gut colonization towards horizontal transfer from the environment to the infants.

Keywords: AMR; antibiotics; antimicrobial resistance genes; gut microbiome; infant microbiome; microbiome; microbiome transmission.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Transmitted species and exclusively shared genes of different adult/mother-infant groups. P values (Wilcoxon rank sum test) for unrelated woman-infant antibiotic-treated group, unrelated woman-infant control group, and paired mother-infant antibiotic-treated group all represent comparisons with the paired mother-infant/child control group. Abbreviations: ESGs, exclusively shared genes.
Figure 2.
Figure 2.
Relative abundance at phylum level.
Figure 3.
Figure 3.
Relative species abundance of children’s fecal samples. Infant samples obtained 3–7 days after birth are shown on the bottom, and samples obtained at 12 months on the top. Species on the left side of the x-axis are species transmitted from the maternal gut microbiome. Only species that with ≥5% relative abundance in any sample are shown. (Individual species and their abundances are available in Supplementary Table 5.)
Figure 4.
Figure 4.
Antimicrobial-resistant (AMR) gene abundance and source of AMR genes in infants’ gut microbiome. The unit of abundance unit is copies per million (the number of reads mapped to the AMR gene per million reads mapped to all genes in the sample). AMR genes in infants transmitted from mothers are not necessarily exclusively shared genes (as listed in Table 1); exclusively shared genes must exist in both mother and infant and must be 100% identical in full gene length. In this figure, an AMR gene in an infant’s sample is considered transmitted if the gene is from a species that can be traced back to the mother’s sample, even if the AMR gene was not found in the mother’s sequencing data.
Figure 5.
Figure 5.
Nonmetric multidimensional scaling (MDS) plot of samples and taxonomic distance between groups. A, X-axis and y-axis are the two MDS dimensions. Each point is a sample. A dashed line connects a mother’s sample to an infant’s sample at 3–7 days after birth, then to that child’s sample at 12 months. The 2 overlapping ellipses cover the mothers’ samples in the control and the antibiotic-treated groups. B, Taxonomic distance (range, 0.0–1.0) between different groups. Both plots were based on Bray-Curtis distance on species relative abundance.

References

    1. Marston HD, Dixon DM, Knisely JM, Palmore TN, Fauci AS. Antimicrobial resistance. JAMA 2016; 316:1193–204.
    1. Schrag SJ, Zywicki S, Farley MM, et al. . Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000; 342:15–20.
    1. Moore MR, Schrag SJ, Schuchat A. Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. Lancet Infect Dis 2003; 3:201–13.
    1. Escobar GJ, Puopolo KM, Wi S, et al. . Stratification of risk of early-onset sepsis in newborns ≥ 34 weeks’ gestation. Pediatrics 2014; 133:30–6.
    1. Fjalstad JW, Stensvold HJ, Bergseng H, et al. . Early-onset sepsis and antibiotic exposure in term infants: a nationwide population-based study in Norway. Pediatr Infect Dis J 2016; 35:1–6.
    1. Gill SR, Pop M, Deboy RT, et al. . Metagenomic analysis of the human distal gut microbiome. Science 2006; 312:1355–9.
    1. Qin J, Li R, Raes J, et al. ; MetaHIT Consortium . A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464:59–65.
    1. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486:207–14.
    1. Lloyd-Price J, Mahurkar A, Rahnavard G, et al. . Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 2017; 550:61–6.
    1. Ferretti P, Pasolli E, Tett A, et al. . Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe 2018; 24:133–45.e5.
    1. Shao Y, Forster SC, Tsaliki E, et al. . Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature 2019; 574:117–21.
    1. Yassour M, Jason E, Hogstrom LJ, et al. . Strain-level analysis of mother-to-child bacterial transmission during the first few months of life. Cell Host Microbe 2018; 24:146–54.e4.
    1. Asnicar F, Manara S, Zolfo M, et al. . Studying vertical microbiome transmission from mothers to infants by strain-level metagenomic profiling. mSystems 2017; 2:e00164-16.
    1. Dardas M, Gill SR, Grier A, et al. . The impact of postnatal antibiotics on the preterm intestinal microbiome. Pediatr Res 2014; 76:150–8.
    1. Tapiainen T, Koivusaari P, Brinkac L, et al. . Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants. Sci Rep 2019; 9:10635.
    1. Yassour M, Vatanen T, Siljander H, et al. . Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 2016; 8:343ra81.
    1. Bokulich NA, Chung J, Battaglia T, et al. . Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med 2016; 8:343ra82.
    1. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Ilmina sequence data. Bioinformatics 2014; 30:2114–20.
    1. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv 2013; 3:13033997.
    1. Nurk S, Meleshko D, Korobeynikov A, Pevzner PA. metaSPAdes: a new versatile metagenomic assembler. Genome Res 2017; 27:824–34.
    1. Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW, Hauser LJ. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics 2010; 11:119.
    1. Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 1999; 27:29–34.
    1. Jia B, Raphenya AR, Alcock B, et al. . CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res 2017; 45:D566–73.
    1. Fu L, Niu B, Zhu Z, Wu S, Li W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 2012; 28:3150–2.
    1. Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22:1658–9.
    1. Otto M. Staphylococcus epidermidis—the ‘accidental’ pathogen. Nat Rev Microbiol 2009; 7:555–67.
    1. Widerström M. Significance of Staphylococcus epidermidis in health care-associated infections, from contaminant to clinically relevant pathogen: this is a wake-up call! J Clin Microbiol 2016; 54:1679–81.
    1. Lax S, Sangwan N, Smith D, et al. . Bacterial colonization and succession in a newly opened hospital. Sci Transl Med 2017; 9:eaah6500.
    1. Otter JA, Yezli S, French GL. The role played by contaminated surfaces in the transmission of nosocomial pathogens. Infect Control Hosp Epidemiol 2011; 32:687–99.
    1. Seale J, Millar M. Perinatal vertical transmission of antibiotic-resistant bacteria: a systematic review and proposed research strategy. BJOG 2014; 121:923–8.
    1. McDonald LC, Bryant K, Snyder J. Peripartum transmission of penicillin-resistant Streptococcus pneumoniae. J Clin Microbiol 2003; 41:2258–60.
    1. Strus M, Pawlik D, Brzychczy-Wloch M, et al. . Group B streptococcus colonization of pregnant women and their children observed on obstetric and neonatal wards of the University Hospital in Krakow, Poland. J Med Microbiol 2009; 58:228–33.
    1. Dubois V, De Barbeyrac B, Rogues AM, et al. . CTX-M-producing Escherichia coli in a maternity ward: a likely community importation and evidence of mother-to-neonate transmission. J Antimicrob Chemother 2010; 65:1368–71.
    1. Tamelienė R, Barčaitė E, Stonienė D, et al. . Escherichia coli colonization in neonates: prevalence, perinatal transmission, antimicrobial susceptibility, and risk factors. Medicina 2012; 48:71–6.
    1. Alicea-Serrano AM, Contreras M, Magris M, Hidalgo G, Dominguez-Bello MG. Tetracycline resistance genes acquired at birth. Arch Microbiol 2013; 195:447–51.
    1. Tullus K, Hörlin K, Svenson SB, Källenius G. Epidemic outbreaks of acute pyelonephritis caused by nosocomial spread of P fimbriated Escherichia coli in children. J Infect Dis 1984; 150:728–36.
    1. Osendarp SJ, van Raaij JM, Darmstadt GL, Baqui AH, Hautvast JG, Fuchs GJ. Zinc supplementation during pregnancy and effects on growth and morbidity in low birthweight infants: a randomised placebo controlled trial. Lancet 2001; 357:1080–5.
    1. Kukkonen K, Savilahti E, Haahtela T, et al. . Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2007; 119:192–8.
    1. Sarvikivi E, Lyytikäinen O, Salmenlinna S, et al. . Clustering of Serratia marcescens infections in a neonatal intensive care unit. Infect Control Hosp Epidemiol 2004; 25:723–9.
    1. Maragakis LL, Winkler A, Tucker MG, et al. . Outbreak of multidrug-resistant Serratia marcescens infection in a neonatal intensive care unit. Infect Control Hosp Epidemiol 2008; 29:418–23.
    1. Schmithausen RM, Sib E, Exner M, et al. . The washing machine as a reservoir for transmission of extended-spectrum-beta-lactamase (CTX-M-15)-producing Klebsiella oxytoca ST201 to newborns. Appl Environ Microbiol 2019; 85:e01435-19.
    1. Korpela K, Salonen A, Virta LJ, et al. . Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun 2016; 7:10410.
    1. Ho NT, Li F, Lee-Sarwar KA, et al. . Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations. Nat Commun 2018; 9:4169.
    1. Pannaraj PS, Li F, Cerini C, et al. . Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr 2017; 171:647–54.
    1. Truong DT, Tett A, Pasolli E, Huttenhower C, Segata N. Microbial strain-level population structure and genetic diversity from metagenomes. Genome Res 2017; 27:626–38.
    1. Truong DT, Franzosa EA, Tickle TL, et al. . MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat Methods 2015; 12:902–3.
    1. Albanese D, Donati C. Strain profiling and epidemiology of bacterial species from metagenomic sequencing. Nat Commun 2017; 8:2260.
    1. Nayfach S, Rodriguez-Mueller B, Garud N, Pollard KS. An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography. Genome Res 2016; 26:1612–25.

Source: PubMed

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