口腔微生物组与肺癌发生、发展的研究现状与展望

Current status and prospects of the relationship between oral microbiome and the occurrence and development of lung cancer

“微生物组在健康和疾病中扮演什么角色?”这一热点话题作为全世界最前沿的125个科学问题之一,近年来持续受到了广泛关注.口腔内含有位点特异性微生物组已是共识,其与宿主细胞的相互作用调节了机体多种生理病理过程.新近证据表明,口腔微生态失调与肺癌风险具有密切的联系,特定口腔微生物及其代谢产物可通过直接/间接的机制在促进或阻延肺癌发生、发展中扮演了重要角色,如诱导炎性微环境、促进肿瘤细胞免疫逃逸和影响细胞相关增殖凋亡信号通路等.上述研究亦支持了口腔微生物在肺癌临床诊疗中的应用潜力.据此,本综述旨在概述口腔微生物组-肺癌研究的前沿进展,探讨当前存在的问题和未来的发展方向,以期激发研究者对这一新兴领域更大的兴趣和更深入的研究.

The occurrence and development of lung cancer involve a complex process that is affected by genetic factors and external stimuli.Lung cancer events induced by environmental factors are more common than those due to genetic factors.The microbiome is an environmental stimulator that plays a vital role in human health and disease,and it has received extensive attention in the past few decades.As one of the most diverse and abundant microbial communities in the human body,the oral microbiome is also the main source of microbes in the lung.When the oral microbiota is unbalanced,the microbial population can be transformed into a pathogenic community that can induce or promote oral and extraoral diseases.Recently,researchers have studied the relationship between the microbiota and lung cancer and found that the microbiome is an environmental factor affecting the occurrence and development of the disease.Poor oral health caused by an imbalance of the oral microbiota increases the risk of lung cancer.Notably,oral microorganisms,such as Porphyromonas gingivalis,Streptococcus,Fusobacterium nucleatum,Veillonella,Aggregatibacter actinomycetemcomitans,and Haemophilus influenzae,are the main oral carcinogenic microorganisms.The mechanisms whereby these oral microbes induce the occurrence and development of lung cancer are mainly through(1)disrupting the biological barrier formed by epithelial cells or through direct inhalation leading to colonization of the lungs,stimulate long-term chronic inflammation,and provide a favorable environment for lung cancer cell proliferation and mutations,or through the colonization of the intestinal tract to affect the function of intestinal flora and promote the growth and proliferation of lung cancer cells.(2)Oral microorganisms can lead to imbalanced immune homeostasis regulation or eliminate the mechanisms of immunity against tumors and promote the escape of tumor cells.They can also lead to pulmonary immune deficiencies and create conditions for the occurrence of cancer.(3)Oral microorganisms can also cause the production of carcinogens,such as reactive oxygen species,thereby affecting cell proliferation and apoptotic signaling pathways and promoting the proliferation,invasion,and metastasis of lung cancer cells.Briefly,these studies support the important application potential of oral microbiota in the clinical diagnosis and treatment of lung cancer.Although many studies have supported a relationship between the oral microbiome and lung cancer,research on the potential mechanisms of action is still in the early stages,and more in-depth investigations are needed.This review discusses the characteristics of the oral microbiota in patients with lung cancer;in vivo and in vitro studies on the oral microbiota and lung cancer;and the prospect of using oral microbiota in the prevention,clinical diagnosis,and treatment of lung cancer.This review aims to provide an overview of the cutting-edge advancements in the field of oral microbiota-lung cancer research,discuss current challenges,and highlight future directions,in order to inspire researchers to develop a greater interest and conduct more in-depth studies in this emerging field.