Gut Microbiota-Derived PGF2α Fights against Radiation-Induced Lung Toxicity through the MAPK/NF-κB Pathway
Zhi-Yuan Chen,
Hui-Wen Xiao,
Jia-Li Dong,
Yuan Li,
Bin Wang,
Sai-Jun Fan,
Ming Cui
Affiliations
Zhi-Yuan Chen
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300110, China
Hui-Wen Xiao
Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Jia-Li Dong
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300110, China
Yuan Li
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300110, China
Bin Wang
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300110, China
Sai-Jun Fan
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300110, China
Ming Cui
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300110, China
Radiation pneumonia is a common and intractable side effect associated with radiotherapy for chest cancer and involves oxidative stress damage and inflammation, prematurely halting the remedy and reducing the life quality of patients. However, the therapeutic options for the complication have yielded disappointing results in clinical application. Here, we report an effective avenue for fighting against radiation pneumonia. Faecal microbiota transplantation (FMT) reduced radiation pneumonia, scavenged oxidative stress and improved lung function in mouse models. Local chest irradiation shifted the gut bacterial taxonomic proportions, which were preserved by FMT. The level of gut microbiota-derived PGF2α decreased following irradiation but increased after FMT. Experimental mice with PGF2α replenishment, via an oral route, exhibited accumulated PGF2α in faecal pellets, peripheral blood and lung tissues, resulting in the attenuation of inflammatory status of the lung and amelioration of lung respiratory function following local chest irradiation. PGF2α activated the FP/MAPK/NF-κB axis to promote cell proliferation and inhibit apoptosis with radiation challenge; silencing MAPK attenuated the protective effect of PGF2α on radiation-challenged lung cells. Together, our findings pave the way for the clinical treatment of radiotherapy-associated complications and underpin PGF2α as a gut microbiota-produced metabolite.