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



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.


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.


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.


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


  • 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 under accession number PRJNA296814.

Code availability

Code is available upon request.


  1. CDC. Achievements in public health, 1900–1999 impact of vaccines universally recommended for children–United States, 1990–1998. (1998).

  2. Chard, A. N. Routine vaccination coverage — worldwide, 2019. MMWR Morb. Mortal. Wkly. Rep. 69, 1706–1710 (2020).

  3. Hill, H. A. Vaccination coverage by age 24 months among children born in 2016 and 2017—National Immunization Survey-Child, United States, 2017–2019. MMWR Morb. Mortal. Wkly. Rep. 68, 913–918 (2020).

  4. Zimmermann, P. & Curtis, N. Factors that influence the immune response to vaccination. Clin. Microbiol. Rev. 32, e00084-18 (2019).

  5. Gensollen, T., Iyer, S. S., Kasper, D. L. & Blumberg, R. S. How colonization by microbiota in early life shapes the immune system. Science 352, 539–544 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res. 30, 492–506 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zhang, Y. et al. Composition of the murine gut microbiome impacts humoral immunity induced by rabies vaccines. Clin. Transl. Med. 10, e161 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Uchiyama, R., Chassaing, B., Zhang, B. & Gewirtz, A. T. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. J. Infect. Dis. 210, 171–182 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lamousé-Smith, E. S., Tzeng, A. & Starnbach, M. N. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS ONE 6, e27662 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lynn, M. A. et al. Early-life antibiotic-driven dysbiosis leads to dysregulated vaccine immune responses in mice. Cell Host Microbe 23, 653.e5–660.e5 (2018).

    Article  Google Scholar 

  11. Oh, J. Z. et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41, 478–492 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Huda, M. N. et al. Stool microbiota and vaccine responses of infants. Pediatrics 134, e362–e372 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Harris, V. C. et al. Significant correlation between the infant gut microbiome and rotavirus vaccine response in rural Ghana. J. Infect. Dis. 215, 34–41 (2017).

    Article  CAS  PubMed  Google Scholar 

  14. Harris, V. et al. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan. Gut Microbes 9, 93–101 (2018).

    Article  CAS  PubMed  Google Scholar 

  15. Gilbert-Diamond, D. et al. Rice consumption contributes to arsenic exposure in US women. Proc. Natl Acad. Sci. USA 108, 20656–20660 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Madan, J. C. et al. Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. JAMA Pediatr. 170, 212 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lundgren, S. N. et al. Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner. Microbiome 6, 109 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pruesse, E. et al. SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res. 35, 7188–7196 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Coker, M. et al. Specific class of intrapartum antibiotics relates to maturation of the infant gut microbiota: a prospective cohort study. BJOG 127, 217–227 (2020).

    Article  CAS  PubMed  Google Scholar 

  21. McIver, L. J. et al. bioBakery: a meta’omic analysis environment. Bioinformatics 34, 1235–1237 (2018).

    Article  CAS  PubMed  Google Scholar 

  22. Beghini, F. et al. Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. eLife 10, e65088 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jódar, L. et al. Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants. Vaccine 21, 3265–3272 (2003).

    Article  PubMed  Google Scholar 

  24. Liang, J. L. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 67, 1–41 (2018).

  25. CDC. Birth 18 years immunization schedule. (2021).

  26. Olarte, L. & Jackson, M. A. Streptococcus pneumoniae. Pediatr. Rev. 42, 349–359 (2021).

    Article  PubMed  Google Scholar 

  27. McCool, T. L., Harding, C. V., Greenspan, N. S. & Schreiber, J. R. B- and T-cell immune responses to pneumococcal conjugate vaccines: divergence between carrier- and polysaccharide-specific immunogenicity. Infect. Immun. 67, 4862–4869 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Genova, G. D., Roddick, J., McNicholl, F. & Stevenson, F. K. Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific. Blood 107, 2806–2813 (2006).

    Article  PubMed  Google Scholar 

  29. Zhao, T. et al. Influence of gut microbiota on mucosal IgA antibody response to the polio vaccine. npj Vaccines 5, 1–9 (2020).

    Article  Google Scholar 

  30. Robertson, R. C. et al. The fecal microbiome and rotavirus vaccine immunogenicity in rural Zimbabwean infants. Vaccine 39, 5391–5400 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fix, J. et al. Association between gut microbiome composition and rotavirus vaccine response among Nicaraguan infants. Am. J. Trop. Med. Hyg. 102, 213–219 (2019).

    Article  PubMed Central  Google Scholar 

  32. Huda, M. N. et al. Bifidobacterium abundance in early infancy and vaccine response at 2 years of age. Pediatrics 143, e20181489 (2019).

  33. Mullié, C. et al. Increased poliovirus-specific intestinal antibody response coincides with promotion of Bifidobacterium longum-infantis and Bifidobacterium breve in infants: a randomized, double-blind, placebo-controlled trial. Pediatr. Res. 56, 791–795 (2004).

    Article  PubMed  Google Scholar 

  34. Kukkonen, K., Nieminen, T., Poussa, T., Savilahti, E. & Kuitunen, M. Effect of probiotics on vaccine antibody responses in infancy – a randomized placebo-controlled double-blind trial. Pediatr. Allergy Immunol. 17, 416–421 (2006).

    Article  PubMed  Google Scholar 

  35. Licciardi, P. et al. Maternal supplementation with LGG reduces vaccine-specific immune responses in infants at high-risk of developing allergic disease. Front. Immunol. 4, 381 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lucas-Hourani, M. et al. Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity. PLoS Pathog. 9, e1003678 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Dimitrova, P. et al. Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes Th2 cell differentiation. J. Immunol. 169, 3392–3399 (2002).

    Article  CAS  PubMed  Google Scholar 

  38. Hubler, M. J. & Kennedy, A. J. Role of lipids in the metabolism and activation of immune cells. J. Nutr. Biochem. 34, 1–7 (2016).

    Article  CAS  PubMed  Google Scholar 

  39. Milani, C. et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol. Mol. Biol. Rev. 81, e00036-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Coker, M. O. et al. Infant feeding alters the longitudinal impact of birth mode on the development of the gut microbiota in the first year of life. Front. Microbiol. 12, 642197 (2021).

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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.


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

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Authors and Affiliations



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.

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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).

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