Lung Injury And Cancer Promotion Of Fine Particulate Matter Depended On Lung Microbiota

Microbiome is one of the important factors for the stability of the host’s internal environment,which is closely associated with metabolism and immunity of the host.However,microbiome dysbiosis is closely related to injury induced by environmental exposure and occurrence/development of several diseases.Nowadays,fine particulate matter(PM2.5)pollution has been a public health issue,which restrained social development.The influence of PM2.5 exposure on microbiome and the role of microbiome in injury and diseases caused by PM2.5 are still unclear.Current study aimed to explore the effects of PM2.5 exposure on the microbiome(lung microbiota and gut microbiota),the role of microbiome in injury and diseases caused by PM2.5,the association between lung microbiota and lung cancer and the role of lung microbiota in lung cancer induced by PM2.5.1.The studies of PM2.5 exposure on lung/gut microbiota and lung metabonomics showed that the subacute PM2.5 exposure caused dysbiosis of lung microbiota and gut microbiota,namely increase of the total amount of microbiota in unit mass of lung/feces,reduction of alpha diversity,significant changes of microbiotal composition and structure,reduction of probiotics and augment of pathogens.Subacute PM2.5 exposure altered the metabonomics of lung tissue,which were associated with significantly changed lung microbiota.The micronucleus rate of polychromatic erythrocytes(PCE)in bone marrow significantly augmented after exposure to PM2.5,suggesting the genomic instability of mice.Tunel experiment of lung tissue and γ-H2AX analysis showed that PM2.5 exposure resulted in significant DNA damage and genomic instability of the lung tissues in mice.2.To investigate the role of lung and gut microbiota in lung damage and genomic instability caused by PM2.5 exposure,we altered the lung and gut microbiota of mice in the exposure group by microbiota transplantation.The results showed that after transplantation of lung/gut microbiota of normal mice,the micronucleus rate of PCE in bone marrow of mice exposed to PM2.5 was not significantly reduced,and systemic inflammation was not significantly improved.Lung microbiota transplantation significantly alleviaviated lung inflammation,cell apoptosis and DNA damage caused by PM2.5 exposure,while gut microbiota transplantation had no significant effect on lung injury caused by PM2.5 exposure.Transplantation of Lactobacillus,Fusobacterium and Shigella also significantly altered lung inflammation,fibrosis and DNA damage caused by PM2.5 exposure.The influence of lung microbiota transplantation on lung damage induced by PM2.5 exposure may be related to the activation of cGAS/STING/TLR9 signaling pathway.3.In order to investigate the correlation between lung microbiota and lung cancer,we conducted a case-control study to analyze the differences of lung microbiota between health controls and lung cancer patients.The data demonstrated an obviously difference in the lung microbiota among lung cancer patients and controls,and the relative abundances of Fusobacterium and Shigella were significantly increased in lung cancer patients.Furthermore,the causal relationship between lung microbiota and lung cancer was confirmed by microbiota transplantation.The results showed that lung microbiota of lung cancer patients accelerated the progression of lung cancer in lung cancer model mice,increased lung cancer cells,and significantly upregulated the expression of lung cancer progression indicators Ki67 and PCNA.To further confirm the role of lung microbiota in accelerating the progression of lung cancer caused by PM2.5 exposure,we used antibiotics to clear the lung microbiota of mice in PM2.5 exposure group,and/or transplanted the lung microbiota of lung cancer patients and controls.The results showed that elimination of lung microbiota in PM2.5 exposed mice with antibiotics could significantly reduce lung cancer progression and inflammation in lung cancer model mice and transplantation of lung microbiota from lung cancer patients significantly increased lung cancer progression,lung tissue inflammation and DNA damage in lung cancer model mice.Transplantation of Lactobacillus,Fusobacterium and Shigella could also significantly alter the progression of lung cancer,lung inflammation and DNA damage caused by PM2.5 exposure.In this study,we observed and analyzed changes in lung/gut microbiota of mice caused by exposure to subacute PM2.5,and confirmed the role of lung/gut microbiota in lung injury,fibrosis and DNA damage caused by exposure to PM2.5 through microbia transplantation.On the other hand,this study analyzed the correlation between lung microbiota and lung cancer,confirmed the causal relationship between lung microbiota and the development of lung cancer through microbiota transplantation,and identified several bacterial indicators of lung cancer.We also analyzed and confirmed the role of lung microbiota in the cancer-promoting effect of PM2.5 via the inflammation and DNA damage caused by lung microbiota.This study analyzed the toxicity of PM2.5 from the perspective of microbiome,and provided a potential target for the diagnosis,prevention and treatment of lung cancer.