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.

Msystems
|August 23, 2023
PubMed

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.
Abstract

Related Concept Videos

Microorganisms in Medicine and Therapeutics01:29

Microorganisms in Medicine and Therapeutics

Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
54
Anatomy of the Intestines01:23

Anatomy of the Intestines

Although digestion of proteins, carbohydrates, and lipids may begin in the stomach, it is completed in the intestine. The absorption of nutrients, water, and electrolytes from food and drink also occurs in the intestine. The intestines can be divided into two structurally distinct organs—the small and large 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...
72.4K
Vaccinations01:51

Vaccinations

Overview
44.7K
Development of Immunocompetence01:22

Development of Immunocompetence

The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
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...
342
Immunological Memory01:23

Immunological Memory

Immunological memory, a pivotal pillar of the adaptive immune system, is responsible for the body's ability to remember and respond more swiftly and effectively to previously encountered pathogens. This remarkable feature is what makes vaccines so effective in preventing diseases.
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...
667
Factors Affecting the Risk of Infection01:26

Factors Affecting the Risk of Infection

The hosts' susceptibility to infection depends on several factors. The integrity of the skin and mucous membranes helps protect the body against microbial attacks. When the skin is altered, the chance of infection, limb loss, and even death increases.
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...
11.9K