Microbial dysbiosis and the host airway epithelial response: insights into HIV-associated COPD using multi'omics profiling

• Published in: Respiratory research 2023-05, Vol.24 (1), p.124-124, Article 124
• Main Authors: Jude, Marcia Smiti, Yang, Chen Xi, Filho, Fernando Studart Leitao, Hernandez Cordero, Ana I, Yang, Julia, Shaipanich, Tawimas, Li, Xuan, Lin, David, MacIsaac, Julie, Kobor, Michael S, Sinha, Sunita, Nislow, Corey, Singh, Amrit, Lam, Wan, Lam, Stephen, Guillemi, Silvia, Harris, Marianne, Montaner, Julio, Ng, Raymond T, Carlsten, Christopher, Paul Man, S F, Sin, Don D, Leung, Janice M
• Format: Article
• Language: English
• Subjects: Airway epithelium; Analysis; Antiviral agents; Biomarkers; Care and treatment; Cellular biology; Chronic obstructive pulmonary disease; Cigarette smoking; COPD; Data integration; Datasets; Diagnosis; Discriminant analysis; Dosage and administration; Dysbacteriosis; Dysbiosis; Dysbiosis - genetics; Epigenetics; Epithelium; Gene Expression Profiling; Gene sequencing; Genes; Health aspects; HIV; HIV Infections - epidemiology; HIV Infections - genetics; HIV patients; Human immunodeficiency virus; Humans; Immune system; Integration; Lung diseases; Lung diseases, Obstructive; Methylation; Microbial activity; Microbiome; Microbiomes; Microorganisms; Mortality; Obstructive lung disease; Phylogenetics; Prevotella; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - genetics; Respiratory tract; RNA sequencing; Taxonomy; Transcriptome; Transcriptomes; Transcriptomics; Variance analysis
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-023-02431-4

People living with HIV (PLWH) are at increased risk of developing Chronic Obstructive Pulmonary Disease (COPD) independent of cigarette smoking. We hypothesized that dysbiosis in PLWH is associated with epigenetic and transcriptomic disruptions in the airway epithelium. Airway epithelial brushings were collected from 18 COPD + HIV + , 16 COPD - HIV + , 22 COPD + HIV - and 20 COPD - HIV - subjects. The microbiome, methylome, and transcriptome were profiled using 16S sequencing, Illumina Infinium Methylation EPIC chip, and RNA sequencing, respectively. Multi 'omic integration was performed using Data Integration Analysis for Biomarker discovery using Latent cOmponents. A correlation > 0.7 was used to identify key interactions between the 'omes. The COPD + HIV -, COPD -HIV + , and COPD + HIV + groups had reduced Shannon Diversity (p = 0.004, p = 0.023, and p = 5.5e-06, respectively) compared to individuals with neither COPD nor HIV, with the COPD + HIV + group demonstrating the most reduced diversity. Microbial communities were significantly different between the four groups (p = 0.001). Multi 'omic integration identified correlations between Bacteroidetes Prevotella, genes FUZ, FASTKD3, and ACVR1B, and epigenetic features CpG-FUZ and CpG-PHLDB3. PLWH with COPD manifest decreased diversity and altered microbial communities in their airway epithelial microbiome. The reduction in Prevotella in this group was linked with epigenetic and transcriptomic disruptions in host genes including FUZ, FASTKD3, and ACVR1B.