Kangli Yang ¹ Shuaifeng Wang ² Zheng Ding ³ Kai Zhang ¹ Weiwei Zhu ⁴ Huifen Wang ⁴ Mengshu Pan ⁵ Xiangnan Li ³ Hongmin Wang ¹ Zujiang Yu ^2,4*

• ¹ Department of Respiratory Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ² Gene Hospital of Henan Province, Center for Precision Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou city, China
• ³ Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
• ⁴ Department of Infectious Diseases, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
• ⁵ Department of Grassroots Medical, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

Background Lung is the largest mucosal area of the human body and directly connected to the external environment, facing microbial exposure and environmental stimuli. Therefore, studying the internal microorganisms of the lung is crucial for a deeper understanding of the relationship between microorganisms and the occurrence and progression of lung cancer. Methods Tumor and adjacent nontumor tissues were collected from 38 lung adenocarcinoma patients and used nanopore sequencing technology to sequence the 16s full-length sequence of bacteria, and combining bioinformatics methods to identify and quantitatively analyze microorganisms in tissues, as well as to enrich the metabolic pathways of microorganisms. Results the microbial composition in lung adenocarcinoma tissues is highly similar to that in adjacent tissues, but the alpha diversity is significantly lower than that in adjacent tissues. The difference analysis results show that the bacterial communities of Streptococcaceae, Lactobacillaceae, and Neisseriales were significantly enriched in cancer tissues. The results of metabolic pathway analysis indicate that pathways related to cellular communication, transcription, and protein synthesis were significantly enriched in cancer tissue. In addition, clinical staging analysis of nicotine exposure and lung cancer found that Haemophilus, paralinfluenzae, Streptococcus gordonii were significantly enriched in the nicotine exposure group, while the microbiota of Cardiobactereae and Cardiobacterales were significantly enriched in stage II tumors. The microbiota significantly enriched in IA-II stages were Neisseriaeae, Enterobacteriales, and Cardiobacterales, respectively. Conclusion Nanopore sequencing technology was performed on the full length 16s sequence, which preliminarily depicted the microbial changes and enrichment of microbial metabolic pathways in tumor and adjacent nontumor tissues. The relationship between nicotine exposure, tumor progression, and microorganisms was explored, providing a theoretical basis for the treatment of lung cancer through microbial targets.