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-α 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.

中文翻译：

---

肠道菌群可通过调节化疗引起的营养不良大鼠的能量代谢来减轻肌肉消耗。

背景技术营养不良是癌症患者化疗后的常见临床症状，其特征在于肌肉消瘦和代谢失调。最近已经研究了肠道菌群对肌肉代谢的调节。但是，没有直接令人信服的证据证明操纵肠道菌群的稳态可以调节化学疗法引起的肌肉代谢紊乱。在这里，我们调查肠道菌群在5-氟尿嘧啶（5-Fu）诱导的营养不良大鼠模型中肌肉代谢调节中的潜在作用。方法将雄性Sprague-Dawley大鼠随机分为两组（n = 8 /组）：对照组和5-Fu组。在5-Fu组中，大鼠通过腹膜内注射接受5-Fu（40 mg / kg /天），共4天，所有大鼠都饲养了8天。营养状况，肌肉功能，评估肌肉代谢产物和肠道菌群。粪便微生物群移植（FMT）被用于探索肠道微生物群对肌肉代谢的潜在调控。结果与对照组相比，接受5-Fu处理的大鼠的体重和食物摄入减少。5-Fu降低了血清中总蛋白和白蛋白的水平，并显着增加了肌肉组织中IL-6和TNF-α的水平。接受5-Fu的大鼠同时表现出肌肉功能和纤维大小的减少。此外，与对照组相比，5-Fu组显示出肠道菌群不同的特征，包括相对较低的Fimicutes丰度和较高的变形杆菌和Verrucomicrobia丰度。两组之间鉴定出14种差异化的肌肉代谢产物，主要与糖酵解，氨基酸代谢，和TCA循环途径。此外，健康大鼠的粪便移植改善了接受5-Fu治疗的大鼠的营养状况和肌肉功能。值得注意的是，FMT可以抑制肌肉中的炎症反应，并逆转5-Fu处理的大鼠中几种差异性肌肉代谢物的变化和能量代谢。结论我们的研究表明，肠道菌群在调节5-Fu引起的营养不良的大鼠的肌肉代谢和促进肌肉能量产生中起着重要作用，表明通过控制肠道菌群的体内平衡可以减轻化学疗法诱导的肌肉消耗。并逆转了5-FU处理的大鼠中几种差异肌肉代谢物和能量代谢的变化。结论我们的研究表明，肠道菌群在调节5-Fu引起的营养不良的大鼠的肌肉代谢和促进肌肉能量产生中起着重要作用，表明通过控制肠道菌群的体内平衡可以减轻化学疗法诱导的肌肉消耗。并逆转了5-FU处理的大鼠中几种差异肌肉代谢物和能量代谢的变化。结论我们的研究表明，肠道菌群在调节5-Fu引起的营养不良的大鼠的肌肉代谢和促进肌肉能量产生中起着重要作用，表明通过控制肠道菌群的体内平衡可以减轻化学疗法诱导的肌肉消耗。