Profile of the Lower Respiratory Tract Microbiome in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome and Lung Disease

Abstract

Once an human immunodeficiency virus (HIV)-infected individual enters the onset period, a variety of opportunistic infections may occur, affecting various systems and organs throughout the body, due to the considerable reduction in the body's immune function. The objectives of this study were to explore the relationship between immune status and microbial communities in the lungs of individuals with HIV infection. A total of 88 patients with lung disease [80 (91%) HIV-positive and 8 (9%) HIV-negative] were enrolled in our study between January and July 2018, and 88 bronchoalveolar lavage fluid (BALF) samples were obtained during bronchoscopy. In this cross-sectional study, we investigated differences in the pulmonary microbiome of patients with HIV who had different immune statuses. The diversity of bacteria in the lungs of HIV-positive individuals was lower than that in HIV-negative individuals (p < 0.05). There was a significant difference in the composition and distribution of bacteria and fungi between the HIV-positive and HIV-negative groups (p < 0.01). The number of fungal species in the BALF of HIV-positive patients was higher than in HIV-negative patients. The diversity of bacteria and fungi in the BALF of HIV-positive patients increased with decreasing CD4 T-cell counts. Linear regression analysis showed that Pneumocystis (R ² = 6.4e-03, p < 0.05), Cryptosphaeria (R ² = 7.2e-01, p < 0.05), Candida (R ² = 3.9e-02, p < 0.05), and Trichosporon (R ² = 7.7e-01, p < 0.05) were negatively correlated with CD4 counts (F-test, p < 0.05). The samples collected from HIV-positive patients exhibited a different pattern relative to those from the HIV-negative group. Differences in host immune status cause differences in the diversity and structure of lower respiratory tract microorganisms.

Keywords: CD4; HIV; bronchoalveolar lavage; lower respiratory tract; microbiota; next-generation sequencing.

FIGURE 1

The diversity of HIV-infected microbiota decreased and the structure of the bacteria changed. (A) Comparison of bacterial alpha diversity in BALF at the genus level between HIV-negative individuals and HIV-positive individuals treated with HAART. (B) Comparison of fungal alpha diversity in BALF fluid at the genus level between HIV-negative individuals and HIV-positive individuals treated with HAART. (C) Principal coordinates analysis (PCoA) using a Bray–Curtis dissimilarity of BALF sample (16S rRNA; n = 88) bacterial community profiles, representatively rarefied to 38,721 reads/sample. (D) Principal coordinates analysis (PCoA) using a Bray–Curtis dissimilarity of BALF sample (ITS rRNA; n = 88) fungal community profiles, representatively rarefied to 58,677 reads/sample. (E) Volcano plots of genus-level taxonomic bins in the 16S rRNA gene datasets. The x-axes display the fold changes in relative abundance (log 2). (F) Volcano plots of genus-level taxonomic bins in the ITS rRNA gene datasets. The x-axes display the fold changes in relative abundance (log 2).

FIGURE 2

The types of microorganisms in the BALF of HIV-positive individuals increase with decreasing CD4 counts. (A) A Venn diagram showing bacterial genus distribution of 16S rRNA for each group (G1 vs. G2 vs. G3 vs. non-HIV). (B) A Venn diagram showing fungal genus distribution of ITS rRNA for each group (G1 vs. G2 vs. G3 vs. non-HIV). (C) Smooth line diagram of the change in the bacterial count target. (D) Smooth line diagram of the change in the fungal count target. (E) Linear model used to describe the relationship between species numbers and CD4 counts.

FIGURE 3

The types of microorganisms in the BALF of HIV-positive individuals increase with decreasing CD4 counts. Profiles of pathogenic microorganisms in HIV/AIDS patients under different immune states. The y-axis coordinate is the CD4 cell count. The x-axis coordinate is a patient at this CD4 value. The text near the curve indicates newly discovered microorganisms at this CD4 value. The numbers in parentheses are the numbers of samples containing the species.