Lower respiratory tract infections (LRTI) remain the leading cause of morbidity and mortality among children under five years globally. The nasopharynx (NP) functions as an interface between the external environment and lower respiratory tract and is a natural niche for commensal as well as pathogenic microbes. A balanced resident NP bacterial community early in life plays a key role in immune education, colonization resistance against respiratory pathogens, and ultimately protection against invasive disease.
We therefore longitudinally studied the NP microbiota in a birth cohort of 1000 South African infants, with fortnightly sampling over the first year of life. The microbiota was assessed using 16S rRNA amplicon sequencing and qPCR targeting 33 potential respiratory pathogens. Active surveillance for LRTI was implemented.
The incidence of LRTI was 0.27 episodes per child year. Pathogens most strongly associated with LRTI were RSV, parainfluenza virus, adenovirus, H. influenzae and B. pertussis. Distinct organism-specific patterns of NP detection in the period prior to LRTI were observed, with adenovirus colonizing infants in the weeks prior to LRTI, while RSV was detected largely only at the time of LRTI. Interactions between pathogens were observed, with interactions between M. catarrhalis and adenovirus, and between coronaviruses and S. pneumoniae associated with LRTI.
Among healthy infants, alpha and beta diversity of the NP microbiome decreased over time, with predictable progression to a microbiome dominated by M. catarrhalis and H. influenzae. This progression was largely independent of environmental determinants. However alpha diversity in the first 6 months of life was associated with gestational age, mode of delivery and maternal smoking, while in the latter half of the first year, diversity was associated with older siblings and daycare attendance. Seasonal variation in the microbiota was observed.