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A prospective study of the infant gut microbiome in relation to vaccine response

Pediatric Research volume 93, pages 725–731 (2023)Cite this article

Abstract

Background

The establishment of the gut microbiome plays a key symbiotic role in the developing immune system; however, its influence on vaccine response is yet uncertain. We prospectively investigated the composition and diversity of the early-life gut microbiome in relation to infant antibody response to two routinely administered vaccines.

Methods

Eighty-three infants enrolled in the New Hampshire Birth Cohort Study were included in the analysis. We collected blood samples at 12 months of age and assayed the isolated serum to quantify total IgG and measured antibody to pneumococcal capsular polysaccharide and tetanus toxoid. Stool samples were collected from infants at 6 weeks of age and sequenced using 16S rRNA, and a subset of 61 samples were sequenced using shotgun metagenomics sequencing.

Results

We observed differences in beta diversity for 16S 6-week stool microbiota and pneumococcal and tetanus IgG antibody responses. Metagenomics analyses identified species and metabolic pathways in 6-week stool associated with tetanus antibody response, in particular, negative associations with the relative abundance of Aeriscardovia aeriphila species and positive associations with the relative abundance of species associated with CDP-diacylglycerol biosynthesis pathways.

Conclusions

The early gut microbiome composition may influence an infant’s vaccine response.

Impact

  • Early intestinal microbiome acquisition plays a critical role in immune maturation and in both adaptive and innate immune response in infancy.

  • We identified associations between early life microbiome composition and response to two routinely administered vaccines—pneumococcal capsular polysaccharide and tetanus toxoid—measured at approximately 1 year of age.

  • Our findings highlight the potential impact of the gut microbiome on infant immune response that may open up opportunities for future interventions.

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Fig. 1: PCoA plots of bacterial 16S V4-V5 rRNA sequencing Bray–Curtis dissimilarity for PCP and TT.
Fig. 2: Associations between metagenomics bacterial species and vaccine response.
Fig. 3: Associations between elastic-net and metabolic pathways and vaccine response.

Data availability

The microbiome data used in this study can be found at http://www.ncbi.nlm.nih.gov/sra under accession number PRJNA296814.

Code availability

Code is available upon request.

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Acknowledgements

We thank all staff and participants of the NHBCS for their contribution to our study. We also thank Vanitha Sampath for her assistance in editing the manuscript.

Funding

This study was supported by the US National Institutes of Health under award numbers NIGMS P20GM104416, NIEHS P42ES007373, NIEHS P01ES022832, and NIEHS R21ES020936.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Yuka Moroishi, Juliette Madan & Margaret R. Karagas

  2. Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Yuka Moroishi & Jiang Gui

  3. Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University School of Medicine, Stanford, CA, USA

    Kari C. Nadeau

  4. Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA, USA

    Hilary G. Morrison

  5. Department of Pediatrics, Children’s Hospital at Dartmouth, Lebanon, NH, USA

    Juliette Madan

Authors
  1. Yuka Moroishi
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  2. Jiang Gui
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  4. Hilary G. Morrison
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  6. Margaret R. Karagas
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Contributions

Y.M., M.R.K., and J.M. contributed to conception of the study. M.R.K., J.M., K.C.N., and H.G.M. contributed to data acquisition and processing. Y.M. and J.G. contributed to statistical analyses. Y.M., M.R.K., J.M., and K.C.N. interpreted results. Y.M. wrote the first manuscript draft. Y.M., M.R.K., J.M., K.C.N., H.G.M., and J.G. reviewed and edited the manuscript.

Corresponding author

Correspondence to Margaret R. Karagas.

Ethics declarations

Competing interests

K.C.N. reports grants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS), and Food Allergy Research & Education (FARE); stock options from IgGenix, Seed Health, ClostraBio, and ImmuneID; is Director of World Allergy Organization (WAO), Advisor at Cour Pharma, Consultant for Excellergy, Red tree ventures, Eli Lilly, and Phylaxis, Co-founder of Before Brands, Alladapt, Latitude, and IgGenix; and National Scientific Committee member at Immune Tolerance Network (ITN), and National Institutes of Health (NIH) clinical research centers, outside the submitted work; patents include “Mixed allergen composition and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” “Methods and assays for detecting and quantifying pure subpopulations of white blood cells in immune system disorders,” and “Methods of isolating allergen-specific antibodies from humans and uses thereof.” All other authors declare no conflicts of interest.

Ethics approval and consent to participate

The Committee for the Protection of Human Subjects at Dartmouth College approved all protocols, and we provided written informed consent to all participants upon enrollment to this study.

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Moroishi, Y., Gui, J., Nadeau, K.C. et al. A prospective study of the infant gut microbiome in relation to vaccine response. Pediatr Res 93, 725–731 (2023). https://doi.org/10.1038/s41390-022-02154-0

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