Bacterial-Derived Outer Membrane Vesicles in Chronic Obstructive Pulmonary Disease and HIV Infection in a Ugandan Population
Abstract
Background: The prevalence of chronic obstructive pulmonary disease (COPD) has increased among people living with HIV (PLWH) despite the global scale-up of antiretroviral therapy (ART). Currently, it is not fully known what drives chronic lung inflammation in the PLWH despite being virologically suppressed on ART. Recent data show that PLWH have an altered lung bacterial biomass. Bacterial outer membrane vesicles (OMVs) secreted by these bacteria may instigate greater immunological derangement than individual bacterial communities. Methods: Induced sputum samples were collected from 40 COPD+ HIV+, 40 COPD− HIV+, 40 COPD+ HIV− and 40 COPD– HIV– participants. 16S sequencing was performed prior to the start of the study. OMVs were processed from the sputum samples using the Norgen Exosome extraction kit, and profiled using a lipopolysaccharide (LPS) ELISA assay. Microbiome data was analysed using QIMME 2 and R. PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)2 programme, which predicts metagenomes from 16S data, Analysis of Compositions of Microbiomes with Bias Correction (ANCOMBC) and Multivariate analysis by linear models (MaAsLin) analysis were used to analyse the relationship between OMV concentration and microbiota profiles. OMV analysis was done using GraphPad Prism 9. Results: Our results show a significant difference in OMV concentrations from COPD+ compared to COPD- participants regardless of HIV status. We detected significant associations between high OMV concentrations and the genera Rothia, Prevotella, Alloscardovia, Actinomyces, Selenomonas and Leptotrichia. No significant differences in the relative abundance, alpha diversity, and beta diversity of any phyla and genera were identified. Similar to OMV concentrations, functional genes associated with LPS biosynthesis, protein export, ATP binding cassette (ABC) transporters and secretion systems were differentially abundant in the HIV-COPD+ and HIV+COPD+, compared to the HIV+COPD-, and HIV-COPD- subgroups. Conclusions: This study demonstrates that bacterial derived OMVs are abundantly present in the airways of participants with COPD. These vesicles could be further explored as potential biomarkers of disease severity or to guide development of drug targets specific to COPD.