NHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.
CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.
Nutr Diabetes. 2021 Jul 31;11(1):27. doi: 10.1038/s41387-021-00169-w.
Trimethylamine-N-oxide (TMAO), a gut-microbiota-dependent metabolite generated from its dietary precursors such as choline, has been identified as an independent risk factor for atherosclerosis. Metformin is the most widely used drug for the treatment of type 2 diabetes (T2D), which has therapeutic effects on hyperglycemia accelerated atherosclerosis. A growing body of evidence suggest that metformin plays a therapeutic role by regulating the structure and metabolic function of gut microbiota. However, whether metformin has an impact on gut-microbiota-mediated TMAO production from choline remains obscure. In this study, the oral administration of metformin significantly reduced choline diet-increased serum TMAO in choline diet-fed C57BL/6J mice. The diversity analysis based on 16S rRNA gene sequencing of C57BL/6J mice fecal samples indicated that metformin markedly changed the gut-microbiota composition. Metformin was positively correlated with the enrichment of different intestinal bacteria such as Bifidobacterium and Akkermansia and a lower cutC (a choline utilization gene) abundance. Furthermore, the ex vivo and in vitro inhibitory effects of metformin on choline metabolism of TMA-producing bacteria were confirmed under anaerobic condition. The results suggested that metformin suppresses serum TMAO level by remodeling gut microbiota involved in TMA generation from choline.
三甲胺 N-氧化物（TMAO）是一种肠道微生物依赖性代谢物，由其膳食前体如胆碱产生，已被确定为动脉粥样硬化的独立危险因素。二甲双胍是治疗 2 型糖尿病（T2D）最广泛使用的药物，它对加速高血糖的动脉粥样硬化有治疗作用。越来越多的证据表明，二甲双胍通过调节肠道微生物群的结构和代谢功能发挥治疗作用。然而，二甲双胍是否对胆碱介导的 TMAO 产生有影响仍不清楚。在这项研究中，口服二甲双胍可显著降低胆碱饮食喂养的 C57BL/6J 小鼠血清 TMAO 水平。基于 C57BL/6J 小鼠粪便样本 16S rRNA 基因测序的多样性分析表明，二甲双胍显著改变了肠道微生物群的组成。二甲双胍与双歧杆菌和 Akkermansia 等不同肠道细菌的富集呈正相关，同时降低了 cutC（一种胆碱利用基因）的丰度。此外，在厌氧条件下，证实了二甲双胍对产 TMA 菌胆碱代谢的体外和体外抑制作用。结果表明，二甲双胍通过重塑参与胆碱生成 TMA 的肠道微生物群来抑制血清 TMAO 水平。
