Very early life microbiome and metabolome correlates with primary vaccination variability in children

Abstract

ABSTRACT Despite multiple vaccine doses early in life, a substantial proportion of infants do not mount protective responses. In this study, we followed a cohort of children over the first 2 years of life, collecting microbiome and metabolome data longitudinally to investigate correlates of lower and higher responses to primary vaccinations. We found that the stool and nasopharyngeal microbiome developed with age, though demonstrated divergent timing and patterns in maturation. When measured at child age 2 months, evenness of genera in the stool microbiome correlated with lower vaccine responses, upregulated metabolome genes that encode for lipid A biosynthesis and oxidative phosphorylation correlated with higher vaccine responses, and abundance of phenylpyruvic acid in serum correlated with lower vaccine responses, measured 10 months later. Antibiotic exposure was associated with low vaccine response, and microbiome/metabolome features at child age 2 months, before childhood vaccinations commenced, correlated with variations in vaccine responses measured at child age 1 year. These results indicate that there may be potential to intervene before first childhood vaccinations to improve later protection. 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.