Bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age

Pediatrics. 2019 Feb;143(2):e20181489. doi: 10.1542/peds.2018-1489.


Background: The intestinal microbiome in early infancy affects immunologic development and thus may affect vaccine memory, though few prospective studies have examined such associations. We examined the association of Bifidobacterium levels in early infancy with memory responses to early vaccination measured at 2 years of age.

Methods: In this prospective observational study, we examined the association of Bifidobacterium abundance in the stool of healthy infants at 6 to 15 weeks of age, near the time of vaccination, with T-cell and antibody responses measured at 6 weeks, 15 weeks, and 2 years of age. Infants were vaccinated with Bacillus Calmette-Guérin (BCG) (at birth), oral polio virus (at birth and at 6, 10, and 14 weeks), tetanus toxoid (TT) (at 6, 10, and 14 weeks), and hepatitis B virus (at 6, 10, and 14 weeks). Fecal Bifidobacterium was measured at 6, 11, and 15 weeks. Bifidobacterium species and subspecies were measured at 6 weeks.

Results: Mean Bifidobacterium abundance in early infancy was positively associated with the CD4 T-cell responses to BCG, TT, and hepatitis B virus at 15 weeks, with CD4 responses to BCG and TT at 2 years, and with plasma TT-specific immunoglobulin G and stool polio-specific immunoglobulin A at 2 years. Similar associations were seen for the predominant subspecies, Bifidobacterium longum subspecies infantis.

Conclusions: Bifidobacterium abundance in early infancy may increase protective efficacy of vaccines by enhancing immunologic memory. This hypothesis could be tested in clinical trials of interventions to optimize Bifidobacterium abundance in appropriate populations.

Trial registration: NCT01583972 NCT02027610.

Publication types

  • Observational Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • BCG Vaccine / administration & dosage*
  • Bifidobacteriales Infections / diagnosis*
  • Bifidobacteriales Infections / epidemiology
  • Bifidobacteriales Infections / prevention & control*
  • Bifidobacterium / drug effects*
  • Bifidobacterium / physiology
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Prospective Studies
  • Treatment Outcome
  • Vaccination / methods*
  • Vaccination / trends


  • BCG Vaccine

Associated data