Interplay of lung microbiome and epigenetics in former smokers: A machine learning and fuzzy logic approach on COPD progression

The progression of Chronic Obstructive Pulmonary Disease (COPD) has been shown in many studies to be directly related to changes in epigenetic modification. This study aims to investigate the relationships between smoking status, lung microbiome dysbiosis, and the long-term effect of smoking persist...

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Main Authors: Hamidreza Taherkhani, Azadeh Kavianfar, Hossein Lanjanian, Nazanin Hosseinkhan, Mahdieh Salimi, Sajjad Nematzadeh, Mohammad Mehdi Naghizadeh, Sadegh Azimzadeh, Ali Masoudi-Nejad
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844025013258
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Summary:The progression of Chronic Obstructive Pulmonary Disease (COPD) has been shown in many studies to be directly related to changes in epigenetic modification. This study aims to investigate the relationships between smoking status, lung microbiome dysbiosis, and the long-term effect of smoking persists even in former smokers. A supervised machine learning algorithm was employed to classify preprocessed 16S rRNA data from 112 COPD patients, identify operational taxonomic units (OTUs), and assess bacterial abundance and diversity. Metabolic models and interactions of key bacteria associated with mortality were further investigated, along with their influence on host epigenetics. Discriminative features related to mortality and the distinction between current smokers and former smokers were successfully identified using features obtained from a fuzzy logic-based model built on the extracted data. A comprehensive microbiome analysis revealed a total of 1781 OTUs, with 13 showing significant differences in abundance and relevance to COPD across 5 phyla. Bacterial metabolic interactions were identified, and a network was constructed by simulating the environment, identifying 379 robust interactions. We observed a decrease in Veillonella abundance during Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) compared to stable clinical periods and a decrease in Veillonellaceae abundance in sputum samples after AECOPD triggered by rhinovirus infection. Notably, the epigenetic changes induced by smoking suggested a long-lasting consequence for cellular function and disease susceptibility even after quitting smoking. We proposed epigenetics as the key to the relationship between anaerobic and aerobic bacteria in the lung microbiome of individuals with COPD. Anaerobic bacteria produce metabolites during fermentation and positively affect aerobic bacteria. By influencing the epigenetic regulation of genes related to the immune response, inflammation, and cell proliferation, these metabolites may contribute to alterations in lung function and the development of COPD even after quitting smoking.
ISSN:2405-8440