Characteristics Of The Microbiome In Lung Tissues From Patients With Pulmonary Tuberculosis And Lung Cancer

Objective:To explore the characteristics of the microbiome in the lung tissues,including lesions of different pathological changes and normal lung areas,from patients with pulmonary tuberculosis and those with lung cancer.Methods:Matched formalin-fixed and paraffin-embedded(FFPE)tissue samples were selected from 20 patients who were diagnosed as pulmonary tuberculosis or lung cancer in Beijing Chest Hospital from 2016 to 2017.The specific regions with necrosis,granuloma,adenocarcinoma,squamous cell carcinoma and normal lung areas were collected using Laser Capture Microdissection system.Characteristics of microbiome were investigated through 16S rRNA High-throughput sequencing.Results:The major phyla in the lung samples of pulmonary tuberculosis patients(relative abundance>1%)were:Proteobacteria,Actinobacteria,Firmicutes,Bacteroidetes and TM7.There was no significant difference in microbial community composition among necrosis,granuloma and normal lung area.However,Firmicutes showed higher relative abundance in necrosis than that in granuloma(Z=-2.100,P=0.036)or normal lung area(Z=-2.380,P=0.017),while TM7 showed higher relative abundance in the normal lung area than that in the necrosis(Z=-2.240,P=0.025).In genus level,9 major groups were detected(relative abundance>1%),including Ochrobactrum,Sphingomonas,Corynebacterium,Brevibacterium,Brevundimonas,Hydrogenophilus,Enhydrobacter,Propionibacterium and Sphingobacterium,There were significant differences in microbial community compositions between granuloma vs normal lung area(F=9.093,P<0.001),and between necrosis vs normal lung area(F=7.683,P<0.001).Ochrobactrum showed higher relative abundance in normal lung area than that in necrosis(Z=-2.380,P=0.017)or granuloma(Z=-2.100,P=0.036).Sphingomonas showed relatively lower abundance in normal lung area than that in necrosis(Z=-2.521,P=0.012)or granuloma(Z=-2.521,P=0.012).Enhydrobacter showed higher relative abundance in necrosis area than that in granuloma(Z=-2.380,P=0.017).In addition,Mycobacterium as a pathogenic bacteria of tuberculosis(relative abundance<1%)showed higher relative abundance in necrosis than that in granuloma(Z=-2.366,P=0.018)or normal lung area(Z=-2.366,P=0.018).The major phyla in the lung samples of lung cancer patients(relative abundance>1%)were:Proteobacteria,Bacteroidetes,Firmicutes,Actinobacteria,Acidobacteria,Cyanobacteria,Verrucomicrobia,Planctomycetes and TM7.There was no significant difference in microbial community composition among adenocarcinoma,squamous cell carcinoma and normal lung area.In genus level,13 major groups were detected(relative abundance>1%),including Ochrobactrum,Pseudomonas,Stenotrophomonas,Brevibacterium,Parabacteroides,Sphingoterium,Lactobacillus,Corynebacterium,Acinetobacter,Natronomonas,Brevundimonas,Sphingomonas and Enhydrobacter.There were significant differences in microbial community compositions between adenocarcinoma vs normal lung area(F=2.151,P=0.024),and between squamous cell carcinoma vs normal lung area(F=3.012,P=0.023).However,Pseudomonas showed higher relative abundance in cancer area than that in normal lung area(Z=-2.197,P=0.028),while Enhydrobacter showed relatively lower abundance in cancer area than that in normal lung area(Z=-2.028,P=0.043).In addition,Proteobacteria?Firmicute?Bacteroidetes?TM7(phyla level)and Sphingobacterium?Sphingomonas?Corynebacterium?Brevundimonas?Enhydrobacter(genus level)showed a significant differences in microbial community compositions between lesion area vs normal lung area.Conclusion:The microbial communities in different areas of lungs from patients with tuberculosis and patients with lung cancer were not significantly different at phylum level,but were significantly different in genus level.These differential bacteria are helpful to further understand the pathogenesis of tuberculosis and lung cancer,but the detailed relationships still need further study.In addition,we also found that there were differences in the distribution of five types of microorganisms in genus level between the two diseases.More study is needed to determine their roles in the future.This study explored the microbiome community in necrosis,granuloma,adenocarcinoma,squamous cell carcinoma and normal lung areas in lungs from patients with tuberculosis and with lung cancer,which may provid a theoretical foundation for clinical prevention,diagnosis and treatment of tuberculosis patients and lung cancer.