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 a consequence of it, is unknown. In order to answer this question, longitudinal studies are needed. Methods: We conducted an analysis of a longitudinal prospective cohort study of 1,981 Zambian mother-infant pairs who underwent NP sampling from 1-week through 14-weeks of age at 2-3-week intervals. Ten of the infants in the cohort developed LRTI and were matched 3:1 with healthy comparators. We completed 16S rRNA gene sequencing on the samples each of these infants contributed, as well as from baseline samples of the infants mothers, and characterized the normal maturation of the healthy infant NP microbiome, compared to infants who developed LRTI. Results: The infant NP microbiome maturation was characterized by transitioning from Staphylococcus 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 NP dysbiosis before infection, in most cases as early as the first week of life. Dysbiosis was characterized by the presence of Novosphingobium,Delftia, high relative abundance of Anaerobacillus, Bacillus, and low relative abundance of Dolosigranulum, compared to the healthy controls. Mothers of infants with LRTI also had low relative abundance of Dolosigranulum in their baseline samples compared to mothers of infants that did not develop an LRTI. Conclusions: Our results suggest that NP microbiome dysbiosis precedes 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 other pathogenic forces that directly lead to LRTI. Funding: This work was supported by The Southern Africa Mother Infant Pertussis Study - Nasopharyngeal Carriage (SAMIPS-NPC). PI Gill. Funder NIH/NIAID (1R01AI133080). WEJ and TF were supported by funds from the NIH, U01CA220413 and R01GM127430.