Study of the Microenvironment of the Lung Flora in Female Lung Adenocarcinoma Patients: From Benign Lesions to Invasive Lung Adenocarcinoma

Background: The number of female lung adenocarcinoma patients is increasing annually, but these patients are difficult to diagnose in the early stage without obvious clinical symptoms, leading to late-stage diagnoses and poor outcomes. Recent studies have shown that the lung microbiota is closely related to the occurrence and development of lung cancer, especially the characteristic changes in the lung microbiota of lung cancer patients, which opens a new research direction for the diagnosis and treatment of lung cancer. This study aimed to analyze the characteristics of the lung flora in different stages of female lung adenocarcinoma. Methods: 16S rRNA sequencing technology was used to analyze the alpha diversity, beta diversity, composition, and function of the pulmonary flora in female patients with benign lesions (n=7), adenocarcinoma in situ (n = 16), microinvasive adenocarcinoma (n = 31), and invasive adenocarcinoma (n = 25). Results: Progression to invasive lung adenocarcinoma is correlated with reduced alpha diversity in the lung flora. Compared with the other stages, only the invasive adenocarcinoma stage had significant differences in the beta diversity of the lung flora. At the phylum and genus levels, the abundance of major flora species decreased significantly as the disease progressed to the invasive adenocarcinoma stage, whereas the abundance of Bacillus spp. increased significantly. The abundance of phenotypes with mobile elements, biofilm-forming ability, oxidative stress tolerance, parthenogenetic anaerobic properties, and pathogenicity was significantly greater in invasive adenocarcinomas. The abundance of metabolic pathways was significantly lower in invasive adenocarcinomas. Conclusions: Invasive adenocarcinoma has a unique flora structure characterized by decreased flora diversity and abundance and an increase in specific flora (e.g., Bacillus). In terms of bacterial function, adaptability and pathogenicity increased, and metabolic pathway activity decreased.