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

Autor: Jude MS; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada., Yang CX; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada., Filho FSL; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada., Hernandez Cordero AI; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada., Yang J; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada., Shaipanich T; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Li X; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada., Lin D; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada., MacIsaac J; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada., Kobor MS; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada., Sinha S; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada., Nislow C; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada., Singh A; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada., Lam W; British Columbia Cancer Research Centre, Vancouver, BC, Canada., Lam S; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; British Columbia Cancer Research Centre, Vancouver, BC, Canada., Guillemi S; British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, Vancouver, BC, Canada.; Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Harris M; British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, Vancouver, BC, Canada.; Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Montaner J; British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, Vancouver, BC, Canada.; Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Ng RT; Department of Computer Science, University of British Columbia, Vancouver, BC, Canada., Carlsten C; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada.; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Paul Man SF; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada.; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Sin DD; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada.; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Leung JM; Centre for Heart Lung Innovation, St. Paul's Hospital, Centre for Heart Lung Innovation, University of British Columbia, Room 166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada. Janice.Leung@hli.ubc.ca.; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Janice.Leung@hli.ubc.ca.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2023 May 04; Vol. 24 (1), pp. 124. Date of Electronic Publication: 2023 May 04.
DOI: 10.1186/s12931-023-02431-4
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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