Cardiovascular Benefits of Empagliflozin Are Associated With Gut Microbiota and Plasma Metabolites in Type 2 Diabetes.
Cardiovascular Benefits of Empagliflozin Are Associated With Gut Microbiota and Plasma Metabolites in Type 2 Diabetes.
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在2型糖尿病中，雌性甲氟嗪的心血管益处与肠道菌群和血浆代谢产物有关。
DOI：
10.1210/clinem/dgac210
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发表时间：
2022-06-16
影响因子：
5.8
通讯作者：
Yuan, Huijuan
中科院分区：
文献类型：
--
作者：
Deng, Xinru;Zhang, Chenhong;Wang, Pengxu;Wei, Wei;Shi, Xiaoyang;Wang, Pingping;Yang, Junpeng;Wang, Limin;Tang, Shasha;Fang, Yuanyuan;Liu, Yalei;Chen, Yiqi;Zhang, Yun;Yuan, Qian;Shang, Jing;Kan, Quane;Yang, Huihui;Man, Hua;Wang, Danyu;Yuan, Huijuan
已报告恩格列净在2型糖尿病（T2 DM）患者中的心血管获益;然而，其潜在机制尚不清楚。我们假设恩格列净的心血管获益与肠道微生物群和血浆代谢物的改变相关，恩格列净可用作有心血管疾病（CVD）风险的T2 DM患者的初始治疗。这项随机化、开放标签、3个月、2组临床试验纳入了76例接受恩格列净（10 mg/d，n = 40）或二甲双胍（1700 mg/d，n = 36）治疗的初治T2 DM伴CVD风险因素患者。 我们研究了与葡萄糖代谢和CVD危险因素相关的临床参数的变化，使用16 S rRNA基因测序的肠道微生物群，以及使用LC-MS的血浆代谢产物。我们发现两组中HbA 1c水平和葡萄糖代谢的缓解显著且相似。然而，仅恩格列净改善了CVD风险因素。治疗1个月后，恩格列净显著重塑了肠道微生物群;这种改变一直维持到试验结束。恩格列净增加了血浆代谢产物（如鞘磷脂）的水平，但降低了甘氨鹅脱氧胆酸盐、顺乌头酸盐和尿酸水平。同时，恩格列净升高了产短链脂肪酸细菌（如罗斯拜瑞氏菌属、真杆菌属和粪杆菌属）的水平，并降低了几种有害细菌（包括土志贺菌属、嗜胆汁菌属和亨格氏菌属）的水平。恩格列净可能是有心血管疾病风险的T2 DM患者的一种上级初始治疗;其心血管获益可能与肠道微生物群和血浆代谢物的变化相关。
Cardiovascular benefits of empagliflozin in patients with type 2 diabetes mellitus (T2DM) have been reported; however, the underlying mechanism remains unknown. We hypothesized that the cardiovascular benefits of empagliflozin are associated with altered gut microbiota and plasma metabolites, and that empagliflozin may be used as an initial treatment for patients with T2DM at risk of cardiovascular diseases (CVDs). This randomized, open-label, 3-month, 2-arm clinical trial included 76 treatment-naïve patients with T2DM and risk factors for CVD who were treated with either empagliflozin (10 mg/d, n = 40) or metformin (1700 mg/d, n = 36). We investigated changes in clinical parameters related to glucose metabolism and CVD risk factors, gut microbiota using 16S rRNA gene sequencing, and plasma metabolites using LC-MS. We found significant and similar reduction in HbA1c levels and alleviation of glucose metabolism in both groups. However, only empagliflozin improved CVD risk factors. Empagliflozin significantly reshaped the gut microbiota after 1 month of treatment; this alteration was maintained until the end of the trial. Empagliflozin increased the levels of plasma metabolites such as sphingomyelin, but reduced glycochenodeoxycholate, cis-aconitate, and uric acid levels. Concurrently, empagliflozin elevated levels of short-chain fatty acid-producing bacteria such as species from Roseburia, Eubacterium, and Faecalibacterium, and reduced those of several harmful bacteria including Escherichia-Shigella, Bilophila, and Hungatella. Empagliflozin may be a superior initial therapy for patients with T2DM at risk of CVDs; its cardiovascular benefits may be associated with shifts in gut microbiota and plasma metabolites.
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影响因子：
14.9
作者：
Klindworth A;Pruesse E;Schweer T;Peplies J;Quast C;Horn M;Glöckner FO
通讯作者：
Glöckner FO
影响因子：
9.3
作者：
Lee DM;Battson ML;Jarrell DK;Hou S;Ecton KE;Weir TL;Gentile CL
通讯作者：
Gentile CL
影响因子：
20.1
作者：
Kelly TN;Bazzano LA;Ajami NJ;He H;Zhao J;Petrosino JF;Correa A;He J
通讯作者：
He J
影响因子：
16.2
作者：
Mueller NT;Differding MK;Zhang M;Maruthur NM;Juraschek SP;Miller ER 3rd;Appel LJ;Yeh HC
通讯作者：
Yeh HC
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP