Alterations of the upper respiratory microbiome among children living with HIV infection in Botswana

Abstract

ABSTRACTBackgroundChildren living with HIV (CLWH) are at high risk of colonization and infection by bacterial respiratory pathogens. Microbes in the upper respiratory microbiome can prevent colonization by these pathogens. The impact of HIV infection on development of the upper respiratory microbiome during childhood is poorly understood.MethodsWe enrolled healthy CLWH (<5 years) and age- and sex-matched HIV-exposed, uninfected (HEU) and HIV-unexposed, uninfected (HUU) children in a cross-sectional study conducted in Botswana. We used shotgun metagenomic sequencing to compare the nasopharyngeal microbiomes of children by HIV status.FindingsOf 143 children, 44 were CLWH, 49 were HEU, and 50 were HUU. Nasopharyngeal microbiome composition differed by HIV status (p=0·043, R2=0·019). The relative abundance ofCorynebacterium pseudodiphtheriticumwas lower in CLWH compared to HEU and HUU children (p=0·01). Among CLWH, a low (<25%) CD4+ cell percentage was associated with microbiome composition (p=0·009, R2=0·042) and lower relative abundances ofCorynebacterium propinquum(p=0·003),C. pseudodiphtheriticum(p=0·007), andDolosigranulum pigrum(p=0·004). The relative abundances ofC. propinquum, C. pseudodiphtheriticumandD. pigrumin the nasopharyngeal microbiome were negatively correlated with the abundances ofStreptococcus pneumoniaeandStaphylococcus aureus.InterpretationCLWH with HIV-associated immunosuppression have altered nasopharyngeal microbiome composition and lower abundances of bacterial species associated with respiratory health during childhood. These findings suggest that the upper respiratory microbiome may contribute to the high risk of bacterial respiratory infections among CLWH.FundingNational Institutes of Health, Duke Center for AIDS Research, Penn Center for AIDS ResearchRESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for research articles published from database inception through November 20, 2022, using the terms (“nasopharyngeal” OR “nasal” OR “upper respiratory”) AND (“HIV” OR “human immunodeficiency virus”) AND (“microbiome” OR “microbiota”) AND (“pediatric” OR “child” OR “children” OR “infants”). This search returned five articles, three of which collected nasopharyngeal specimens from children living with HIV (CLWH). The objective of two of these articles was pathogen identification using culture- and polymerase chain reaction-based methods. The remaining study characterized the nasopharyngeal microbiomes of children with pneumonia, children with upper respiratory infections, and healthy children in Botswana using 16S rRNA sequencing. Genera associated with respiratory health were less abundant in CLWH with pneumonia, but no data was available for healthy CLWH. Thus, it remained unknown if the microbiome alterations observed in CLWH were associated with HIV or with pneumonia.Added value of this studyTo our knowledge, this is the first study to investigate the nasopharyngeal microbiome in healthy CLWH using metagenomic sequencing. To account for shifts in the microbiome that occur with age, we enrolled age- and sex-matched HIV-exposed, uninfected and HIV-unexposed children for each CLWH. The use of shotgun metagenomic sequencing allowed us to investigate differences in the microbiome at the species level. We found that HIV infection and HIV-associated immunosuppression were associated with an altered nasopharyngeal microbiome and a lower abundance of species associated with respiratory health and resistance to colonization by common bacterial respiratory pathogens.Implications of all the available evidenceThese findings suggest that HIV-associated alterations in the nasopharyngeal microbiome may predispose CLWH to colonization by bacterial respiratory pathogens responsible for invasive infection and death. Strategies to reduce pathogen colonization through modification of the microbiome hold promise for reducing infectious morbidity and mortality in CLWH.