【摘要】 目的：近年来有证据提示肠道可能是二甲双胍的主要作用部位，但二甲双胍对肠道菌群影响的相关研究尚不多，二甲双胍对短链/中链脂肪酸等肠道菌群代谢产物的影响也不明确。本研究拟探讨二甲双胍对高脂喂养大鼠肠道菌群及短链/中链脂肪酸的影响和代谢益处。方法：将24只Sprague-Dawley大鼠随机分为3组：1)正常饮食组(ND组)，普通饲料喂养；2)高脂饮食组(HFD组)，高脂饲料喂养；3)高脂饮食+二甲双胍治疗组(HFD+Met组)，高脂饲料喂养8周，第9周起每日用二甲双胍溶液(150 mg/kg体重)灌胃。实验结束后处死所有大鼠并留取血清、肝脏及结肠内容物标本，检测糖脂代谢指标、肝脏病理、肠道菌群和结肠内容物中的短链/中链脂肪酸水平。结果：二甲双胍显著改善了高脂饮食诱导的糖脂代谢紊乱及肝损伤。与HFD组比较，HFD+Met组Blautia,Romboutsia,Bilophila,Bacteroides菌属丰度降低，Lactobacillus菌属丰度显著增高(均P<0.05)；结肠内容物中丁酸、2-甲基丁酸、戊酸、辛酸和月桂酸水平均显著增高(均P<0.05)，乙酸、异庚酸和壬酸水平均显著降低(均P<0.05)。Spearman相关性分析显示：Lactobacillus菌属丰度与大鼠的体重增量和胰岛素抵抗呈显著负相关，丁酸盐和戊酸盐水平与大鼠胰岛素抵抗、肝损伤呈显著负相关(均P<0.05)。结论：二甲双胍显著增加了高脂饮食大鼠结肠内容物中Lactobacillus等益生菌的丰度，促进了丁酸盐、戊酸盐、月桂酸等短链/中链脂肪酸的产生，提示二甲双胍通过肠道菌群调节机体代谢。更多还原

【Abstract】 Objective: Recent evidence suggests that the gut may be a primary site of metformin action. However, studies on the effects of metformin on gut microbiota remain limited, and its impact on gut microbial metabolites such as short-/medium-chain fatty acids is unclear. This study aims to investigate the effects of metformin on gut microbiota, short-/mediumchain fatty acids, and associated metabolic benefits in high-fat diet rats.Methods: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: 1) Normal diet group(ND group), fed standard chow; 2) high-fat diet group(HFD group), fed a high-fat diet; 3) high-fat diet + metformin treatment group(HFD+Met group), fed a high-fat diet for 8 weeks, followed by daily intragastric administration of metformin solution(150 mg/kg body weight) starting in week 9. At the end of the experiment, all rats were sacrificed, and serum, liver, and colonic contents were collected for assessment of glucose and lipid metabolism, liver pathology, gut microbiota composition, and the concentrations of short-/medium-chain fatty acids.Results: Metformin significantly improved HFD-induced glucose and lipid metabolic disorders and liver injury. Compared with the HFD group, the HFD+Met group showed reduced abundance of Blautia, Romboutsia, Bilophila, and Bacteroides, while Lactobacillus abundance significantly increased(all P<0.05). Colonic contents of butyric acid, 2-methyl butyric acid, valeric acid, octanoic acid, and lauric acid were significantly elevated(all P<0.05), whereas acetic acid, isoheptanoic acid, and nonanoic acid levels were significantly decreased(all P<0.05). Spearman correlation analysis revealed that Lactobacillus abundance was negatively correlated with body weight gain and insulin resistance, while butyrate and valerate levels were negatively correlated with insulin resistance and liver injury(all P<0.05).Conclusion: Metformin significantly increases the abundance of beneficial bacteria such as Lactobacillus and promotes the production of short-/medium-chain fatty acids including butyric, valeric, and lauric acid in the colonic contents of HFD rats, suggesting that metformin may regulate host metabolism through modulation of the gut microbiota.更多还原