INTERNATIONAL CONGRESS OF
CancerGenetics
Alteration of Lung Microbiota in Smokers and its Association with Lung Cancer Development
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Samane Salehi,1,*
1. Department of Food Biotechnology, Faculty of Agriculture, University of Tabriz, Tabriz, Iran
- Introduction: The human lung, once thought to be a sterile environment, is now recognized as a complex ecosystem hosting diverse microbial communities. This lung microbiota plays an essential role in maintaining pulmonary health and immune homeostasis. However, alterations in the lung microbiome have been associated with various respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, and lung cancer. Smoking is one of the leading causes of lung microbiota dysbiosis, which may contribute to cancer development. Cigarette smoke contains over 7,000 chemicals, many of which are toxic or carcinogenic. These substances can disturb the natural lung microbiota, leading to bacterial imbalances, immune dysregulation, chronic inflammation, and an environment conducive to tumorigenesis. This review focuses on how smoking alters the lung microbiota and how these alterations contribute to the transition from a healthy state to cancerous conditions.
- Methods: For this review, a systematic search of existing literature was conducted using databases such as PubMed, Scopus, and Google Scholar. Studies from the last 5 years were considered to evaluate how smoking-induced changes in the lung microbiome correlate with lung cancer development. Search terms included "lung microbiota," "lung microbiome dysbiosis," "smoking," "cigarette smoke and microbiome," and "lung cancer." Articles were screened for relevance, and only those that explicitly examined lung microbiota changes in smokers, ex-smokers, or lung cancer patients were included. A total of 20 studies were reviewed, focusing on the characterization of lung microbiota in smokers and their potential association with oncogenesis.
- Results: Several studies have documented significant shifts in the composition of the lung microbiota in smokers compared to non-smokers. In healthy individuals, the lung microbiome is dominated by phyla such as Bacteroidetes, Firmicutes, and Proteobacteria. However, in smokers, there is a noticeable increase in the abundance of pathogenic bacteria such as Streptococcus, Neisseria, and Haemophilus, which are associated with inflammation and infection. Simultaneously, beneficial bacteria, including those from the genera Prevotella and Veillonella, are significantly reduced in smokers. These shifts lead to a pro-inflammatory environment, promoting tissue damage, immune suppression, and abnormal cell growth. Chronic exposure to cigarette smoke promotes a state of continuous inflammation and oxidative stress, which facilitates lung tissue damage. Smoking also alters the mucosal immune system by impairing normal clearance mechanisms, such as the mucociliary escalator, which allows pathogens to persist in the lung environment. Alterations in microbial diversity and function were found to enhance the activity of pro-carcinogenic pathways, including those involving NF-kB and STAT3, leading to uncontrolled cell proliferation and impaired immune surveillance. One key mechanism linking smoking-induced microbiota changes to cancer is the overrepresentation of Proteobacteria in the lungs of smokers. Proteobacteria, including Haemophilus and Pseudomonas, produce various virulence factors, including lipopolysaccharides (LPS), which contribute to chronic inflammation and create a microenvironment conducive to cancer development. Studies also found that Neisseria, another bacterial genus elevated in smokers, is associated with increased lung cancer risk through its ability to promote inflammatory signaling. Another important finding from these studies is that microbial dysbiosis persists even after smoking cessation. While quitting smoking does reduce inflammation and improve lung function over time, ex-smokers still harbor a microbiota profile that differs significantly from that of non-smokers. This residual dysbiosis may explain why former smokers remain at higher risk for lung cancer, even decades after quitting. Notably, long-term changes in bacterial diversity and composition may contribute to carcinogenesis through persistent inflammation and immune dysregulation. Additionally, several studies report a significant correlation between specific microbial species and the presence of lung cancer. For example, an increase in Acinetobacter, Rothia, and Streptococcus species was observed in lung cancer patients compared to healthy controls, suggesting these bacteria may play a role in tumor development or progression. Furthermore, the presence of certain bacterial metabolites and by-products in the lung microenvironment can promote DNA damage and inhibit apoptosis, further accelerating the cancerous transformation of lung epithelial cells.
- Conclusion: This review highlights the critical link between smoking-induced alterations in lung microbiota and the development of lung cancer. By disrupting the natural balance of lung microbial communities, smoking creates a pro-inflammatory environment conducive to cancer initiation and progression. Understanding the microbial dynamics in the lungs of smokers and their potential as biomarkers or therapeutic targets may pave the way for novel preventive and treatment strategies in lung cancer management. References Yu, H., et al. (2023). The composition of lung microbiome in lung cancer: a systematic review and meta-analysis. BMC Microbiology, 21(1), 1-10. Zhao, H., et al. (2021). The lung microbiome in COPD and lung cancer: Exploring the potential of metal-based drugs. International Journal of Molecular Sciences, 22(15), 8044. Wang, Y., et al. (2023). The human microbiome: A promising target for lung cancer treatment. Frontiers in Immunology, 14, 1325. Wu, J., et al. (2022). The lung microbiota in cancer: A review. Cancer Letters, 550, 138126. Huang, Y., et al. (2021). The role of the lung microbiome in lung cancer: A systematic review. Journal of Thoracic Oncology, 16(10), 1549-1558. Chen, Y., et al. (2022). The lung microbiome and its association with lung cancer: A review. Clinical and Experimental Pharmacology and Physiology, 49(12), 1135-1144. Li, X., et al. (2023). The lung microbiome and its role in lung cancer: A review. Cancer Management Research, 15, 61-72.
- Keywords: Lung Cancer; Lung Microbiota; Cigarette
