BACKGROUND Obesity is a major problem worldwide and severely affects public safety. As a metabolite of gut microbiota, endogenous butyric acid participates in energy and material metabolism. Considering the serious side effects and weight regain associated with existing weight loss interventions, novel strategies are urgently needed for prevention and treatment of obesity. RESULTS In the present study, we engineered Bacillus subtilis SCK6 to exhibited enhanced butyric acid production. Compared to the original Bacillus subtilis SCK6 strain, the genetically modified BsS-RS06550 strain had higher butyric acid production. The mice were randomly divided into four groups: a normal diet (C) group, a high-fat diet (HFD) group, an HFD + Bacillus subtilis SCK6 (HS) group and an HFD + BsS-RS06550 (HE) group. The results showed BsS-RS06550 decreased the body weight, body weight gain, and food intake of HFD mice. BsS-RS06550 had beneficial effects on blood glucose, insulin resistance and hepatic biochemistry. After the 14-week of experiment, fecal samples were collected for nontargeted liquid chromatography-mass spectrometry analysis to identify and quantify significant changes in metabolites. Sixteen potentially significant metabolites were screened, and BsS-RS06550 was shown to potentially regulate disorders in glutathione, methionine, tyrosine, phenylalanine, and purine metabolism and secondary bile acid biosynthesis. CONCLUSIONS In this study, we successfully engineered Bacillus subtilis SCK6 to have enhanced butyric acid production. The results of this work revealed that the genetically modified live bacterium BsS-RS06550 showed potential anti-obesity effects, which may have been related to regulating the levels of metabolites associated with obesity. These results indicate that the use of BsS-RS06550 may be a promising strategy to attenuate obesity.

中文翻译：

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工程化的产生丁酸盐的细菌可防止高脂饮食诱发的小鼠肥胖。

背景技术肥胖是全世界的主要问题，并且严重影响公共安全。作为肠道微生物的代谢产物，内源性丁酸参与能量和物质代谢。考虑到与现有的减肥干预措施相关的严重的副作用和体重减轻，迫切需要新的策略来预防和治疗肥胖症。结果在本研究中，我们对枯草芽孢杆菌SCK6进行了改造，以提高丁酸的产生。与原始枯草芽孢杆菌SCK6菌株相比，转基因BsS-RS06550菌株具有更高的丁酸产量。将小鼠随机分为四组：正常饮食（C）组，高脂饮食（HFD）组，HFD +枯草芽孢杆菌SCK6（HS）组和HFD + BsS-RS06550（HE）组。结果显示BsS-RS06550降低了HFD小鼠的体重，体重增加和食物摄入。BsS-RS06550对血糖，胰岛素抵抗和肝生化有有益作用。经过14周的实验后，收集粪便样品进行非目标液相色谱-质谱分析，以鉴定和量化代谢产物的显着变化。筛选了十六种潜在的重要代谢物，并显示BsS-RS06550可能调节谷胱甘肽，蛋氨酸，酪氨酸，苯丙氨酸，嘌呤代谢和继发性胆汁酸生物合成中的疾病。结论在这项研究中，我们成功地设计了枯草芽孢杆菌SCK6以提高丁酸的产量。这项工作的结果表明，转基因活细菌BsS-RS06550具有潜在的抗肥胖作用，这可能与调节肥胖相关的代谢产物水平有关。这些结果表明，使用BsS-RS06550可能是减轻肥胖的一种有前途的策略。