Jin Jin, Wang Jiani, Cheng Ruyue, Ren Yan, Miao Zhonghua, Luo Yating, Zhou Qingqing, Xue Yigui, Shen Xi, He Fang, Tian Haoming
Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Microbiol. 2022 Aug 15;13:908327. doi: 10.3389/fmicb.2022.908327. eCollection 2022.
This study aimed to evaluate the possible anti-obesity effects of orlistat and ezetimibe and determine the mechanism by which they alter the composition of gut microbiota and short-chain fatty acids (SCFAs) in mice with a high-fat diet (HFD)-induced obesity. Eighty male, specific pathogen-free C57BL/6J mice aged 3 weeks were divided into four groups ( = 20). The NCD group was fed with a normal diet, and the HFD, HFD+ORL, and HFD+EZE groups were fed with HFD for 20 weeks. From the 13th week onward, the HFD+ORL and HFD+EZE groups were administered with orlistat and ezetimibe, respectively. The glucose and lipid metabolism of the tested mice were evaluated by analyzing blood biochemical indicators during the intervention. Furthermore, the changes in the structure of the fecal microbiota and the fecal SCFA content were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry, respectively. HFD induced the obesity phenotype in mice. Compared to the HFD group, the body weight, visceral fat-to-body weight ratio, serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and oral glucose tolerance test (OGTT) of the HFD+ORL group significantly decreased, whereas fecal butyric acid levels significantly increased. Ezetimibe intervention significantly reduced the OGTT, serum TC, and HDL-C levels only. The α-diversity of the gut microbiota significantly decreased after intervention with orlistat and ezetimibe. Orlistat altered the relative abundance of some bacteria in the fecal microbiota. The populations of , and decreased, whereas those of and significantly increased. Ezetimibe caused changes only in some low-abundance bacteria, as manifested by a decrease in and , and an increase in . The administration of orlistat and ezetimibe can characteristically influence the body weight and serum lipid metabolism, and glucolipid levels in diet-induced obese mice and is accompanied by significant changes in the gut microbiota and SCFAs. These results suggest that the two drugs might exert their own specific anti-obesity effects by modulating the gut microbiota in a different manner. The enhanced health-promoting effect of orlistat might result from its stronger ability to alter the gut microbiota and SCFAs, at least partly.
本研究旨在评估奥利司他和依折麦布可能的抗肥胖作用，并确定它们改变高脂饮食（HFD）诱导肥胖小鼠肠道微生物群组成和短链脂肪酸（SCFAs）的机制。将80只3周龄的雄性无特定病原体C57BL/6J小鼠分为四组（每组n = 20）。正常对照组喂食正常饮食，高脂饮食组、高脂饮食+奥利司他组和高脂饮食+依折麦布组喂食高脂饮食20周。从第13周起，高脂饮食+奥利司他组和高脂饮食+依折麦布组分别给予奥利司他和依折麦布。在干预期间，通过分析血液生化指标评估受试小鼠的糖脂代谢。此外，分别通过16S rRNA测序和气相色谱-质谱法分析粪便微生物群结构和粪便SCFA含量的变化。高脂饮食诱导小鼠出现肥胖表型。与高脂饮食组相比，高脂饮食+奥利司他组的体重、内脏脂肪与体重比、血清总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）以及口服葡萄糖耐量试验（OGTT）均显著降低，而粪便丁酸水平显著升高。依折麦布干预仅显著降低了OGTT、血清TC和HDL-C水平。奥利司他和依折麦布干预后肠道微生物群的α多样性显著降低。奥利司他改变了粪便微生物群中一些细菌的相对丰度。拟杆菌属、普雷沃菌属和瘤胃球菌属的数量减少，而双歧杆菌属和阿克曼菌属的数量显著增加。依折麦布仅引起一些低丰度细菌的变化，表现为嗜胆菌属和脱硫弧菌属减少，而颤螺菌属增加。给予奥利司他和依折麦布可特异性影响饮食诱导肥胖小鼠的体重和血清脂质代谢以及糖脂水平，并伴有肠道微生物群和SCFAs的显著变化。这些结果表明，这两种药物可能通过以不同方式调节肠道微生物群发挥各自特定 的抗肥胖作用。奥利司他增强的健康促进作用可能至少部分源于其更强的改变肠道微生物群和SCFAs的能力。
