The Lung Microbiome of Ugandan HIV-Infected Pneumonia Patients Is Compositionally and Functionally Distinct from That of San Franciscan Patients

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.

The role of the microbiome in exacerbations of chronic lung diseases

“…Of the eight culture-independent studies across three disease states that have compared patients' respiratory specimens acquired at baseline and during exacerbation, all have found no change in bacterial density or community diversity during exacerbation 21, 29, 30, 81, 82, 100-102 . This differs starkly from studies of bacterial pneumonia, in which (as expected) increased inflammation is strongly associated with increases in bacterial burden and decreases in community diversity 36, 103 . The airway inflammation common to all respiratory exacerbations is surprisingly dissociated from microbial load and community domination by one or few pathogenic species.…”

“…All have been remarkably consistent in their key findings: CF exacerbations are not associated with increased bacterial density and are not associated with decreased community diversity (Figures 4B, 4C). These results differ starkly from those found in patients with bacterial pneumonia, for which, as expected, bacterial burden is high, community diversity is low, and the intensity of the host inflammatory response correlates tightly with bacterial burden 16, 103 . These findings, considered with the lack of association between culture-identified pathogens and clinical response summarized above, strongly challenge the conventional understanding of CF exacerbations as acute infections of the airways.…”

Multicenter Comparison of Lung and Oral Microbiomes of HIV-infected and HIV-uninfected Individuals

“…It is important to note that all subject groups in this study were clinically well at the time of enrollment and sampling. Very different results are observed during episodes of clinical pneumonia and with decreased CD4 counts (35).…”

The Lung Microbiome and Airway Disease

“…More recent studies of the airway microbiota have attempted to assess the immune responses associated with microbiota differentials. For example, Iwai and colleagues examined the bacterial communities detected in the bronchoalveolar lavage fluid of 60 Ugandan HIV-infected patients with acute pneumonia (27). Using DNA and RNA extracted in parallel, the authors profiled both the bacterial community composition and, in parallel, the expression of a range of host immune genes (inflammatory cytokines [IL-6, IL-17, tumor necrosis factor-a, IL-4, and IL-13]; a mucin production gene; indoleamine 2,3-dioxygenase, associated with impaired mucosal immunity and increased microbial translocation; and matrix metalloproteinase-9, abundant in lung diseases and involved in the breakdown of extracellular matrix).…”