Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Lett. 2024 Aug 28;598:217096. doi: 10.1016/j.canlet.2024.217096. Epub 2024 Jul 4.
Metabolic derivatives of numerous microorganisms inhabiting the human gut can participate in regulating physiological activities and immune status of the lungs through the gut-lung axis. The current well-established microbial metabolites include short-chain fatty acids (SCFAs), tryptophan and its derivatives, polyamines (PAs), secondary bile acids (SBAs), etc. As the study continues to deepen, the critical function of microbial metabolites in the occurrence and treatment of lung cancer has gradually been revealed. Microbial derivates can enter the circulation system to modulate the immune microenvironment of lung cancer. Mechanistically, oncometabolites damage host DNA and promote the occurrence of lung cancer, while tumor-suppresive metabolites directly affect the immune system to combat the malignant properties of cancer cells and even show considerable application potential in improving the efficacy of lung cancer immunotherapy. Considering the crosstalk along the gut-lung axis, in-depth exploration of microbial metabolites in patients' feces or serum will provide novel guidance for lung cancer diagnosis and treatment selection strategies. In addition, targeted therapeutics on microbial metabolites are expected to overcome the bottleneck of lung cancer immunotherapy and alleviate adverse reactions, including fecal microbiota transplantation, microecological preparations, metabolite synthesis and drugs targeting metabolic pathways. In summary, this review provides novel insights and explanations on the intricate interplay between gut microbial metabolites and lung cancer development, and immunotherapy through the lens of the gut-lung axis, which further confirms the possible translational potential of the microbiome metabolome in lung cancer treatment.
肠道中栖息的大量微生物的代谢产物可以通过肠-肺轴参与调节肺部的生理活动和免疫状态。目前已确定的微生物代谢产物包括短链脂肪酸(SCFAs)、色氨酸及其衍生物、多胺(PAs)、次级胆汁酸(SBAs)等。随着研究的不断深入,微生物代谢产物在肺癌的发生和治疗中的关键作用逐渐被揭示。微生物衍生产物可以进入循环系统,调节肺癌的免疫微环境。从机制上讲,致癌代谢物会损害宿主 DNA 并促进肺癌的发生,而肿瘤抑制性代谢物则直接影响免疫系统,对抗癌细胞的恶性特性,甚至在改善肺癌免疫治疗的疗效方面显示出相当大的应用潜力。考虑到肠-肺轴的相互作用,深入研究患者粪便或血清中的微生物代谢产物将为肺癌的诊断和治疗选择策略提供新的指导。此外,针对微生物代谢产物的靶向治疗有望克服肺癌免疫治疗的瓶颈,并缓解不良反应,包括粪便微生物移植、微生态制剂、代谢产物合成和靶向代谢途径的药物。总之,本综述通过肠-肺轴的视角,为肠道微生物代谢物与肺癌发生、发展和免疫治疗之间的复杂相互作用提供了新的见解和解释,进一步证实了微生物组代谢组在肺癌治疗中的可能转化潜力。
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