Nasopharyngeal Dysbiosis Precedes the Development of Lower Respiratory Tract Infections in Young Infants, a Longitudinal Infant Cohort Study

Background: Infants suffering from lower respiratory tract infections (LRTIs) have distinct nasopharyngeal (NP) microbiome profiles that correlate with severity of disease. Whether these profiles precede the infection or are a consequence of it, is unknown. In order to answer this question, longitudinal studies are needed.

Methods: We conducted a retrospective analysis of NP samples collected in a longitudinal birth cohort study of Zambian mother-infant pairs. Samples were collected every two weeks from 1-week through 14-weeks of age. Ten of the infants in the cohort who developed LRTI were matched 1:3 with healthy comparators. We completed 16S rRNA gene sequencing on the samples each of these infants contributed and compared the NP microbiome of the healthy infants to infants who developed LRTI.

Results: The infant NP microbiome maturation was characterized by transitioning from dominant to respiratory-genera dominant profiles during the first three months of life, similar to what is described in the literature. Interestingly, infants who developed LRTI had distinct NP microbiome characteristics before infection, in most cases as early as the first week of life. Their NP microbiome was characterized by the presence of , high relative abundance of , and low relative abundance of compared to the healthy controls. Mothers of infants with LRTI also had low relative abundance of in their baseline samples compared to mothers of infants that did not develop an LRTI.

Conclusions: Our results suggest that specific characteristics of the NP microbiome precede LRTI in young infants and may be present in their mothers as well. Early dysbiosis may play a role in the causal pathway leading to LRTI or could be a marker of underlying immunological, environmental, or genetic characteristics that predispose to LRTI.