Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid
Kai-Yue He,
Xin-Yuan Lei,
Dan-Hui Wu,
Lei Zhang,
Jun-Qi Li,
Qiu-Tong Li,
Wei-Tao Yin,
Zi-Long Zhao,
Huai Liu,
Xiong-Yan Xiang,
Ling-Jun Zhu,
Cui-Yun Cui,
Ke-Ke Wang,
Jin-Hua Wang,
Lin Lv,
Qian-Hui Sun,
Guo-Long Liu,
Zhi-Xiang Xu,
Yong-Ping Jian
Affiliations
Kai-Yue He
School of Life Sciences, Henan University, Kaifeng, Henan, China
Xin-Yuan Lei
School of Life Sciences, Henan University, Kaifeng, Henan, China
Dan-Hui Wu
School of Life Sciences, Henan University, Kaifeng, Henan, China
Lei Zhang
School of Life Sciences, Henan University, Kaifeng, Henan, China
Jun-Qi Li
School of Life Sciences, Henan University, Kaifeng, Henan, China
Qiu-Tong Li
School of Life Sciences, Henan University, Kaifeng, Henan, China
Wei-Tao Yin
School of Life Sciences, Henan University, Kaifeng, Henan, China
Zi-Long Zhao
School of Life Sciences, Henan University, Kaifeng, Henan, China
Huai Liu
School of Life Sciences, Henan University, Kaifeng, Henan, China
Xiong-Yan Xiang
School of Life Sciences, Henan University, Kaifeng, Henan, China
Ling-Jun Zhu
School of Life Sciences, Henan University, Kaifeng, Henan, China
Cui-Yun Cui
Department of Blood Transfusion, Henan Provincial People’s Hospital, Zhengzhou, Henan, China
Ke-Ke Wang
Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Jin-Hua Wang
Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Lin Lv
Department of Medical Oncology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
Qian-Hui Sun
School of Life Sciences, Henan University, Kaifeng, Henan, China
Guo-Long Liu
Department of Medical Oncology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
Zhi-Xiang Xu
School of Life Sciences, Henan University, Kaifeng, Henan, China
Yong-Ping Jian
School of Life Sciences, Henan University, Kaifeng, Henan, China
ABSTRACTIntestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.
