Abstract
Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome was significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population.
Highlights
Emerging evidence in the nascent, though rapidly evolving field of human microbiome research has consistently demonstrated the presence of polymicrobial communities on mucosal surfaces, including the respiratory tract [1,2,3,4,5]
A total of 2,671 taxa belonging to 42 phyla were detected in at least one of the 60 Ugandan bronchoalveolar lavage (BAL) samples examined; of these, only 33 taxa were common to all 60 subjects
We examined the cohort for detection of seven of the most common bacterial pulmonary pathogens detected in HIV-infected patients: Pseudomonas aeruginosa, Haemophilus influenzae, Staphylococcus aureus, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Streptococcus pneumoniae and Legionella pneumophila were detected in 49, 10, 1, 0, 0, 0 and 0 of the subjects, respectively
Summary
Emerging evidence in the nascent, though rapidly evolving field of human microbiome research has consistently demonstrated the presence of polymicrobial communities on mucosal surfaces, including the respiratory tract [1,2,3,4,5]. Moving beyond description of these communities, a number of recent studies have demonstrated relationships between microbiome composition and features of pulmonary disease [3,6], implicating the airway microbiome in respiratory disease pathogenesis. We have previously demonstrated that HIV-infected patients with acute pneumonia possess relatively diverse lower airway microbial communities comprised of multiple distinct taxa, including many known pathogens associated with HIV-infected populations [4]. Even in the absence of acute respiratory infection, the lower airways of HIV-infected patients exhibit the presence of a relatively diverse bacterial community [10]. Healthy subjects exhibit little evidence of microbial presence at this site [3,10], indicating that HIV-infection, which itself is a risk factor for developing pulmonary infection, is associated with lower airway colonization by microbial species
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