Characterization of longitudinal nasopharyngeal microbiome patterns in maternally HIV-exposed Zambian infants

Abstract

Background: Previous studies of infants born to HIV-positive mothers have linked HIV exposure to poor outcomes from gastrointestinal and respiratory illnesses, and to overall increased mortality rates. The mechanism behind this is unknown, but it is possible that differences in the nasopharyngeal (NP) microbiome between HIV-unexposed and HIV-exposed infants could play a role in perpetuating some outcomes. Methods: We conducted a longitudinal analysis of 170 NP swabs of healthy HIV-exposed, uninfected (HEU; n=10) infants and their HIV(+) mothers and HIV-unexposed, uninfected (HUU; n=10) infants and their HIV(-) mothers. These swabs were identified from a sample library collected in Lusaka, Zambia between 2015 and 2016. Using 16S rRNA gene sequencing, we characterized the maturation of the microbiome over the first 14 weeks of life to determine what quantifiable differences exist between HEU and HUU infants, and what patterns are reflected in the mothers' NP microbiomes. Results: In both HEU and HUU infants, Staphylococcus and Corynebacterium began as primary colonizers of the NP microbiome but were in time replaced by Dolosigranulum, Streptococcus, Moraxella and Haemophilus. When studying differences between infants, the microbe Staphylococcus haemolyticus indicated a distinctive high association with HIV exposure at birth, even when accounting for the interaction between HIV exposure status and time of sampling. When comparing infants to their mothers with paired analyses, HEU infants’ NP microbiome composition was only slightly different from their HIV(+) mothers at birth or 14 weeks, including in their carriage of S. pneumoniae, H. influenzae, and S. haemolyticus. Conclusions: Our analyses indicate that the HEU infants in our study exhibit subtle differences in the NP microbial composition throughout the sampling interval. Given our results and the sampling limitations of our study, we believe that further research must be conducted in order to confidently understand the relationship between HIV exposure and infants’ NP microbiomes.