Respiratory Tract Oncobiome in Lung Carcinogenesis: Where Are We Now?

SIMPLE SUMMARY: Research has clearly shown a connection between the respiratory tract microbiome and lung cancer. The composition and metabolism of the bacterial community in lung cancer patients differ from those in healthy individuals. Further large-scale studies are needed to understand the microbiome’s role in lung cancer, including identifying bacterial species, deciphering mechanisms and relationships with the macro-organisms, and addressing analysis-related issues. Large-scale research is also needed on the lung mycobiome and virome. Identifying microorganisms involved in oncogenic processes could improve lung cancer patient screening, diagnosis, and therapeutic options. This review presents the current state of knowledge on the role of the respiratory tract microbiome in lung carcinogenesis. We highlight what we know and what we don’ yet know about the human lung oncobiome. ABSTRACT: The importance of microbiota in developing and treating diseases, including lung cancer (LC), is becoming increasingly recognized. Studies have shown differences in microorganism populations in the upper and lower respiratory tracts of patients with lung cancer compared to healthy individuals, indicating a link between dysbiosis and lung cancer. However, it is not only important to identify “which bacteria are present” but also to understand “how” they affect lung carcinogenesis. The interactions between the host and lung microbiota are complex, and our knowledge of this relationship is limited. This review presents research findings on the bacterial lung microbiota and discusses the mechanisms by which lung-dwelling microorganisms may directly or indirectly contribute to the development of lung cancer. These mechanisms include influences on the host immune system regulation and the local immune microenvironment, the regulation of oncogenic signaling pathways in epithelial cells (causing cell cycle disorders, mutagenesis, and DNA damage), and lastly, the MAMPs-mediated path involving the effects of bacteriocins, TLRs signaling induction, and TNF release. A better understanding of lung microbiota’s role in lung tumor pathology could lead to identifying new diagnostic and therapeutic biomarkers and developing personalized therapeutic management for lung cancer patients.