Related Experiment Video
Updated: Jul 18, 2025

Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Very early life microbiome and metabolome correlates with primary vaccination variability in children
Michael Shaffer1, Katharine Best1, Catherine Tang1
1Exploratory Science Center, Merck & Co., Inc. , Cambridge, Massachusetts, USA.
Insights
Early life gut and respiratory microbiome development differs, impacting vaccine response. Bacterial components may enhance vaccine protection, while oxidative stress may reduce it.
Area of Science:
- Microbiome research
- Immunology
- Pediatric health
Background:
- The early life microbiome plays a critical role in immune system development.
- Antibiotic exposure can disrupt microbial communities and potentially impair vaccine efficacy.
- Understanding factors influencing infant immune responses to vaccination is crucial for public health.
Purpose of the Study:
- To investigate the distinct maturation patterns of the gut and nasopharyngeal microbiomes in infants.
- To explore the relationship between early-life microbiome composition, antibiotic exposure, and vaccine responsiveness.
- To identify microbial and metabolic factors associated with varying levels of vaccine-induced antibodies.
Main Methods:
- Simultaneous analysis of stool and nasopharyngeal samples to characterize microbiome composition.
- Assessment of early-life antibiotic exposure history.
- Measurement of vaccine-induced antibody levels.
- Quantification of serum metabolites, including phenylpyruvic acid.
Main Results:
- Stool and nasopharyngeal microbiomes exhibit divergent maturation timelines and compositions.
- Early-life antibiotic exposure may negatively impact vaccine responsiveness.
- Bacteria producing lipopolysaccharide (a TLR4 agonist) in the gut and/or nasopharynx may enhance vaccine protection.
- Infants with lower vaccine-induced antibody levels show increased serum phenylpyruvic acid, suggesting higher oxidative stress.
Conclusions:
- Local mucosal factors influence the distinct development of the gut and respiratory microbiomes.
- The early-life microbiome, particularly the presence of specific bacterial components, may serve as a natural adjuvant, improving vaccine efficacy.
- Metabolic alterations, such as increased oxidative stress, are associated with diminished vaccine responses in infants.
Importance:
We show that simultaneous study of stool and nasopharyngeal microbiome reveals divergent timing and patterns of maturation, suggesting that local mucosal factors may influence microbiome composition in the gut and respiratory system. Antibiotic exposure in early life as occurs commonly, may have an adverse effect on vaccine responsiveness. Abundance of gut and/or nasopharyngeal bacteria with the machinery to produce lipopolysaccharide-a toll-like receptor 4 agonist-may positively affect future vaccine protection, potentially by acting as a natural adjuvant. The increased levels of serum phenylpyruvic acid in infants with lower vaccine-induced antibody levels suggest an increased abundance of hydrogen peroxide, leading to more oxidative stress in low vaccine-responding infants.
Related Concept Videos
Microorganisms in Medicine and Therapeutics
Anatomy of the Intestines
Small Intestines
The small intestine is an ~7 meter-long tube with an inner diameter of just 2.5 cm. Since most nutrients are absorbed here, the inner lining of the...
Vaccinations
Development of Immunocompetence
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
Immunological Memory
What is Immunological Memory?
Immunological memory is an integral function of the immune system that allows it to recognize and react more rapidly and effectively to pathogens previously encountered. This feature...
Factors Affecting the Risk of Infection
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...

