Infant Gut Microbiome and Infections and Symptoms: A Prospective Cohort Study

Background: Emerging evidence points to a critical role of developing gut microbiome on immune maturation and infant health; however as yet, epidemiologic studies are limited to experimental studies, high risk cohorts and cross-sectional analyses. We examined whether infant gut microbiota related to the occurrence of health outcomes such as infections, eczema, and allergy during the first year of life.

Methods: Infants from the prospective New Hampshire Birth Cohort Study were studied. We applied generalized estimating equations to 16S rRNA V4-V5 gene sequencing data from stool samples of 465 infants and shotgun metagenomics sequencing data from185 infants at approximately 6 weeks of age.

Results: Higher alpha diversity associated with increased risk of infection or respiratory symptoms (RR: 1.39; 95% CI: 1.10-1.77) and specifically upper respiratory tract infections (RR: 1.40; 95% CI: 1.12-1.76). After stratifying by delivery mode, we observed increased relative risk of number of infections and symptoms, upper RTI, wheeze, and diarrhea in vaginally delivered infants in relation to increased microbial alpha diversity at 6 weeks of life. Metagenomics analyses identified several microbial species, including Veillonella, Streptococcus, and Clostridium species, as associated with immune-related outcomes.

Conclusion: Our findings in a large prospective birth cohort in the US suggest that early intestinal microbial diversity and abundance of specific key species of the gut microbiome may influence infants’ risks of infection and symptoms such as wheeze and diarrhea. Clarifying patterns in the early life microbiome that may predict adverse immune mediated health outcomes provide opportunities for microbial focused interventions to improve lifelong health.