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Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery

Nature Medicine volume 23, pages 314326 (2017) | Download Citation

Abstract

Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal–infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R2 = 0.038), this was not true for neonatal stool (meconium; Mann–Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P < 0.001, R2 = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.

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Acknowledgements

The authors gratefully acknowledge the support of the NIH Director's New Innovator Award (DP2 DP21DP2OD001500; K.M. Aagaard), the NIH–NINR (NR014792-01; K.M. Aagaard), the NIH National Children's Study Formative Research (N01-HD-80020; K.M. Aagaard), the Burroughs Welcome Fund Preterm Birth Initiative (K.M. Aagaard), the March of Dimes Preterm Birth Research Initiative (K.M. Aagaard), the Baylor College of Medicine Medical Scientist Training Program (NIH NIGMS T32 GM007330; D.C. and K.M. Aagaard), the National Institute of General Medical Sciences (T32GM088129; D.M.C.), Baylor Research Advocates for Student Scientists (D.M.C.) and the Human Microbiome Project funded through the NIH Director's Common Fund at the National Institutes of Health (as part of NIH RoadMap 1.5; K.M. Aagaard). All sequencing and adaptation of protocols for WGS sequencing were performed by the Baylor College of Medicine Human Genome Sequencing Center (BCM–HGSC), which is funded by direct support from the National Human Genome Research Institute (NHGRI) at NIH (U54HG004973 (BCM); R. Gibbs, Principal Investigator). The authors also thank the staff members who were directly involved in clinical recruitment and specimen processing (M. Moller, B. Boggan, R. Benjamin, J. Chen, C. Cook and D. Racusin). The authors are grateful to M. Belfort, J. Versalovic, T. Savidge, R.A. Luna, D. Racusin, M. Suter and K. Meyer for critical review of the manuscript.

Author information

Affiliations

  1. Department of Obstetrics and Gynecology, Division of Maternal–Fetal Medicine, Baylor College of Medicine, Houston, Texas, USA.

    • Derrick M Chu
    • , Jun Ma
    • , Amanda L Prince
    • , Kathleen M Antony
    • , Maxim D Seferovic
    •  & Kjersti M Aagaard
  2. Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA.

    • Derrick M Chu
    •  & Kjersti M Aagaard
  3. Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas, USA.

    • Derrick M Chu
    •  & Kjersti M Aagaard
  4. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

    • Kjersti M Aagaard
  5. Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas, USA.

    • Kjersti M Aagaard

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Contributions

D.M.C. and K.M. Aagaard designed and conceived the study; K.M. Aagaard and K.M. Antony assembled the cohort and developed the infrastructure to obtain swabs, samples and clinical metadata from all samples; K.M. Aagaard and K.M. Antony recruited and sampled all subjects; A.L.P., D.M.C. and M.D.S. prepared samples for sequencing of the gene encoding16S rRNA and for WGS sequencing; D.M.C., J.M. and K.M. Aagaard performed and supervised all analysis and statistical modeling; and D.M.C. and K.M. Aagaard wrote the manuscript, with contributions from J.M., A.L.P., K.M. Antony and M.D.S.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Kjersti M Aagaard.

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https://doi.org/10.1038/nm.4272

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