The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats

doi:10.1007/s00280-020-04060-w

	The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats
	Chen, Haitao 2; Xu, Chao 3; Zhang, Fan 2; Liu, Yu 1; Guo, Yong 4; Yao, Qinghua 3
刊名	CANCER CHEMOTHERAPY AND PHARMACOLOGY
	2020-05-15
关键词	Chemotherapy Malnutrition Gut microbiota Muscle metabolism Fecal microbiota transplantation
ISSN号	0344-5704
DOI	10.1007/s00280-020-04060-w
通讯作者	Guo, Yong(guoyong1047@163.com) ; Yao, Qinghua(Yaoqh@zjec.org.cn)
英文摘要	Background Malnutrition is a common clinical symptom in cancer patients after chemotherapy, which is characterized by muscle wasting and metabolic dysregulation. The regulation of muscle metabolism by gut microbiota has been studied recently. However, there is no direct convincing evidence proving that manipulating gut microbiota homeostasis could regulate muscle metabolic disorder caused by chemotherapy. Here, we investigate the potential role of gut microbiota in the regulation of the muscle metabolism in 5-fluorouracil (5-Fu)-induced malnutrition rat model. Methods Male Sprague-Dawley rats were randomly divided into two groups (n = 8/group): control group and 5-Fu group. In the 5-Fu group, rats received 5-Fu (40 mg/kg/day) by intraperitoneal injection for 4 days, and all rats were raised for 8 days. Nutritional status, muscle function, muscle metabolites, and gut microbiota were assessed. Fecal microbiota transplantation (FMT) was applied to explore the potential regulation of gut microbiota on muscle metabolism. Results 5-Fu-treated rats exhibited loss of body weight and food intake compared to control group. 5-Fu decreased the levels of total protein and albumin in serum, and significantly increased the levels of IL-6 and TNF-alpha in muscle tissue. Rats that received 5-Fu displayed concurrent reduction of muscle function and fiber size. Moreover, 5-Fu group showed a distinct profile of gut microbiota compared to control group, including the relative lower abundance of Firmicutes and a higher abundance of Proteobacteria and Verrucomicrobia. Fourteen differential muscle metabolites were identified between two groups, which were mainly related to glycolysis, amino acid metabolism, and TCA cycle pathway. Furthermore, fecal transplantation from healthy rats improved nutritional status and muscle function in 5-Fu-treated rats. Notably, FMT inhibited the inflammatory response in muscle, and reversed the changes of several differential muscle metabolites and energy metabolism in 5-Fu-treated rats. Conclusions Our study demonstrated that gut microbiota played an important role in the regulation of muscle metabolism and promoting muscle energy production in 5-Fu-induced malnutrition rats, suggesting the potential attenuation of chemotherapy-induced muscle wasting by manipulating gut microbiota homeostasis.
资助项目	Chinese Medicine Key Research Program of Zhejiang Province[2017ZZ004] ; Chinese Medicine Research Program of Zhejiang Province[2019ZA018]
WOS关键词	5-FLUOROURACIL-INDUCED INTESTINAL MUCOSITIS ; SKELETAL-MUSCLE ; PROTEIN ; PROFILES ; CACHEXIA
WOS研究方向	Oncology ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000533054100001
资助机构	Chinese Medicine Key Research Program of Zhejiang Province ; Chinese Medicine Research Program of Zhejiang Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103241]
专题	中国科学院合肥物质科学研究院
通讯作者	Guo, Yong; Yao, Qinghua
作者单位	1.Zhejiang Univ, Coll Life Sci, Hangzhou 310000, Zhejiang, Peoples R China 2.Zhejiang Chinese Med Univ, Clin Coll 1, Hangzhou 310053, Zhejiang, Peoples R China 3.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Integrated Tradit Chinese & Western Med, Hangzhou 310022, Zhejiang, Peoples R China 4.Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Oncol, Hangzhou 310003, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Chen, Haitao,Xu, Chao,Zhang, Fan,et al. The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2020.
APA	Chen, Haitao,Xu, Chao,Zhang, Fan,Liu, Yu,Guo, Yong,&Yao, Qinghua.(2020).The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats.CANCER CHEMOTHERAPY AND PHARMACOLOGY.
MLA	Chen, Haitao,et al."The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats".CANCER CHEMOTHERAPY AND PHARMACOLOGY (2020).