Childhood vaccinations are standard in early childcare and are important for maintaining health in the beginning life stages.1 However, vaccine-induced protection in young children can be variable, leaving some infants unprotected against serious infectious diseases.2 There are many factors that can influence vaccine responses, including genetics, maternal antibodies, and geographical location.3 Researchers showed that the gut microbiome plays a major role in shaping the early infant immune system as well as the vaccine immune response.4,5 However, the link between the method by which a gut microbiome is established during birth and its effect on the childhood vaccine response remains to be established.
Susana Fuentes is a professor at the Centre for Infectious Disease Control in the National Institute for Public Health and the Environment in the Netherlands. While Fuentes was working on the microbiome and its relation to the immune system, she was surrounded by immunologists working on vaccine responses. “I saw two very separate people working on the impact of birth mode on microbiome and people working on the immunology of the national immunization program on children, and I was always intrigued to put the two together,” said Fuentes. In a recent study published in Nature Communications, Fuentes and her colleagues, in a collaboration with Debby Bogaert at the University of Edinburgh, used human infant cohorts born at term to investigate how the delivery mode–vaginal or c-section–affected the microbiome and influenced vaccine responses.6
To investigate the association of delivery, the microbiome, and early vaccine response, Fuentes and her colleagues followed a cohort of 120 healthy infants. Formation of the early infant immune system is partially governed by the gut microbiome, which is seeded at birth.7 The method by which an infant is born influences what types of bacteria are more prevalent in the early microbiome.8 The researchers characterized the infants’ early gut microbiome through genetic sequencing and their mucosal antibody responses following administration of the anti-pneumococcal vaccine at 12 months and the anti-meningococcal vaccine at 18 months of age. They then investigated factors such as mode of delivery, early feeding methods, sex, having pets or siblings, exposure to antibiotics, and daycare attendance on the microbiome and antibody responses.
This investigation presented a considerable challenge because the microbiome can be influenced by many different factors. “Do you even have enough information to correct for everything else that is happening around [them]? Because we’re not isolated from the world. So, they have brothers and sisters, they have pets, they use a pacifier, are bottle fed, breastfed, all these factors. It’s always very challenging,” said Fuentes.
Despite these challenges, the researchers showed that birth by vaginal delivery resulted in higher antibody responses against the anti-pneumococcal and anti-meningococcal vaccines. This could be because the vaginal microbiome is an important microbial source that drives infant gut microbiome development.9 Fuentes further found that the presence of Bifidobacterium and Escherichia coli in the first few weeks of infant gut development resulted in increased immune responses to the vaccines. This study is the first to show an association between gut microbial colonization patterns early in life and the vaccine response, establishing the microbiome as a novel player that researchers can exploit when designing new intervention strategies for infectious diseases.
“I think it really puts another nail in the coffin [in the debate whether] microbes really do influence immune system development in early life,” said Brett Finlay, a professor and microbiologist at the University of British Columbia who was not involved in the study. “And that’s what a vaccination is, it’s a readout of the immune system.”
Fuentes and her colleagues will continue investigating the microbiome and vaccination. In the future, Fuentes hopes that modifying the microbiome with temporary methods, such as diet or probiotics, will boost vaccine responses.
- Maurice JM, et al. State of the world’s vaccines and immunization. 3rd ed. Geneva: World Health Organization; 2009.
- Grassly NC, et al. Biological challenges to effective vaccines in the developing world. Philos Trans R Soc Lond B Biol Sci. 2015;370(1671):20140138.
- Zimmermann P, Curtis N. Factors that influence the immune response to vaccination. Clin Microbiol Rev. 2019;32(2):e00084-18.
- Olin A, et al. Stereotypic immune system development in newborn children. Cell. 2018;174(5):1277-1292.e14.
- Lynn MA, et al. Early-life antibiotic-driven dysbiosis leads to dysregulated vaccine immune responses in mice. Cell Host Microbe. 2018;23(5):630-660.e5.
- de Koff EM, et al. Mode of delivery modulates the intestinal microbiota and impacts the response to vaccination. Nat Commun. 2022;13:6638.
- Bokulich N, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016;8(343):343ra82.
- Mitchell CM, et al. Delivery mode affects stability of early infant gut microbiota. Cell Rep Med. 2020;1(9):100156.
- Dunn AB, et al. The maternal infant microbiome: Considerations for labor and birth. MCN Am J Matern Child Nurs. 2017;42(6):318-325.