Decreased microbiome diversity in the HIV small airway epithelium

Stella Xu,Sunita Sinha,Julia Yang,Stephen Lam,Tawimas Shaipanich,Corey Nislow,Marc A Sze,Amy Tsai,S F Paul Man,Julio Montaner,Wan Lam,Janice M Leung,Marianne Harris,Don D Sin,Silvia Guillemi,Emily A Vucic

doi:10.1186/s12931-018-0835-7

Abstract

BackgroundPersons living with human immunodeficiency virus (PLWH) face an increased burden of chronic obstructive pulmonary disease (COPD). Repeated pulmonary infections, antibiotic exposures, and immunosuppression may contribute to an altered small airway epithelium (SAE) microbiome.MethodsSAE cells were collected from 28 PLWH and 48 HIV- controls through bronchoscopic cytologic brushings. DNA extracted from SAE cells was subjected to 16S rRNA amplification and sequencing. Comparisons of alpha and beta diversity between HIV+ and HIV- groups were performed and key operational taxonomic units (OTUs) distinguishing the two groups were identified using the Boruta feature selection after Random Forest Analysis.ResultsPLWH demonstrated significantly reduced Shannon diversity compared with HIV- volunteers (1.82 ± 0.10 vs. 2.20 ± 0.073, p = 0.0024). This was primarily driven by a reduction in bacterial richness (23.29 ± 2.75 for PLWH and 46.04 ± 3.716 for HIV-, p < 0.0001). Phyla distribution was significantly altered among PLWH, with an increase in relative abundance of Proteobacteria (p = 0.0003) and a decrease in Bacteroidetes (p = 0.0068) and Firmicutes (p = 0.0002). Six discriminative OTUs were found to distinguish PLWH from HIV- volunteers, aligning to Veillonellaceae, Fusobacterium, Verrucomicrobiaceae, Prevotella, Veillonella, and Campylobacter.ConclusionsCompared to HIV- controls, PLWH’s SAE microbiome is marked by reduced bacterial diversity and richness with significant differences in community composition.

Highlights

Persons living with human immunodeficiency virus (PLWH) face an increased burden of chronic obstructive pulmonary disease (COPD)
Lozupone et al found that the abundance of Tropheryma whipplei was significantly increased in bronchoalveolar lavage (BAL) samples of PLWH compared with Human immunodeficiency virus (HIV)- control subjects [4], while a second study by Beck et al showed no differences between the two groups [5]
A third study evaluating BAL demonstrated that PLWH who had advanced disease (CD4 cell counts < 500 cells/mm3) had significantly reduced microbiome diversity when compared to HIV- controls, with diversity starting to return to normal levels once antiretroviral therapy (ART) was initiated [6]

Summary

Introduction

Persons living with human immunodeficiency virus (PLWH) face an increased burden of chronic obstructive pulmonary disease (COPD). A third study evaluating BAL demonstrated that PLWH who had advanced disease (CD4 cell counts < 500 cells/mm3) had significantly reduced microbiome diversity when compared to HIV- controls, with diversity starting to return to normal levels once ART was initiated [6]. While these studies have offered the first insights into the HIV lung microbiome, the reliance on BAL fluid may fail to identify important changes at the specific initial site of injury in

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Conclusion