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Huang, Jia Yi

University of British Columbia

Background: Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of death worldwide and people living with human immunodeficiency virus (HIV, PLWH) are at a higher risk of developing COPD. However, methods to predict adverse events in COPD are limited and lack precision, especially for PLWH. Previously, patterns of COPD microbial dysbiosis and methylation disruptions have been observed in PLWH with COPD. In this study, we hypothesize that increased risk of mortality is associated with microbiome dysbiosis and differential methylation patterns in the airway epithelium of PLWH with COPD. Methods: Airway epithelial samples from PLWH with (n=32) and without COPD (n=23) and non-HIV infected individuals with (n=35) and without COPD (n=57) were profiled using 16S rRNA sequencing and the Illumina Infinium MethylationEPIC BeadChip. Vital status was captured in the three-year period following bronchoscopy. Microbiome composition and diversity, CpG sites, and methylation age were compared between samples from deceased and survived individuals to identify mortality predictors. Using elastic net regression models, classification models for all-cause mortality were generated using detected features and optimized using the area under the receiver operating characteristics curve (AUC-ROC). Results: We observed a significant increase in alpha diversity in deceased COPD individuals compared to survived participants (p=0.0228), while no difference was observed in PLWH deceased and survived groups (p=0.302). Several pathogens were found to be associated with mortality, including Streptococcus and Veillonella. Top differentially methylated CpG sites associated with death corresponded to cancer-regulating genes, cancer-related pathways and longevity-related pathways. The genus-level microbiome biomarker panel showed promising performance in predicting mortality, especially in PLWH (AUC = 0.875), while the methylation biomarker panel had a weaker AUC performance score of 0.705. Conclusion: Microbial and methylation disturbances in the airway epithelium are associated with mortality in COPD and HIV, with microbiome features demonstrating better predictive performance compared to methylation.

Text

2023-04-19

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/84320

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/