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 infants who are HIV-unexposed or HIV-exposed could play a role in perpetuating some outcomes.

Methods: We conducted a longitudinal analysis of 170 NP swabs of healthy infants who are HIV-exposed (n=10) infants and their HIV(+) mothers, and infants who are HIV-unexposed, uninfected (HUU; n=10) .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 HIV-exposed and HUU infants, and what patterns are reflected in the mothers' NP microbiomes.

Results: In both HIV-exposed 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 evaluating the interaction between HIV exposure status and time of sampling among infants, the microbe Staphylococcus haemolyticus showed a distinctive high association with HIV exposure at birth. When comparing infants to their mothers with paired analyses, HIV-exposed 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 HIV-exposed 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.

Keywords: HIV exposure; children; longitudinal cohort study; microbial communities; nasopharyngeal microbiome.

Figure 1.

The maturation over 17 weeks of the NP microbiomes of A) healthy HIV-exposed (n=10) and HUU infants (n=10) and B) HIV(+) (n=10) and HIV(-) mothers (n=10). These stacked bar plots reveal variation in the relative abundance of microbes between groups of either infants or mothers clustered at the genus level. Each bar represents a single time point binned by age and is the average of ~10 samples. Genera with an average relative abundance of <1% across all samples are labeled as “Other.” The alluvial plot in C) depicts the changing presence of genera across all infant samples by HIV exposure status. As relative abundances change over time, the position of a flow stream representing a single genus may change position relative to the other genera.

Figure 2.. Plots of estimated marginal means of the abundance of a given microbe, given the estimated GEE effects of time point of sampling (x axis) and HIV status (line color).

A line illustrates the estimated change in microbe abundance over time, with positive or negative slopes illustrating increased or decreased estimated abundance in log CPM (respectively). HIV-exposed infants (denoted as HEU) are depicted in blue, and HIV-unexposed, uninfected infants (HUU) are depicted in red. Given the separate lines for each status and changing slope across time, these plots depict the interaction effect between time point and HIV status. All microbes had at least marginally significant time effects, but only S. haemolyticus had a very strong HIV exposure status effect.