二甲双胍调节菌群以降血糖并延缓衰老的机制(综述)

二甲双胍可以重塑菌群组成,降低多种衰老相关疾病发病率并改善二型糖尿病;
二甲双胍可增加黏液产生菌(Akk菌)、短链脂肪酸产生菌等的丰度,降低具核梭杆菌及厚壁菌门的丰度;
二甲双胍可通过调节菌群增加胰岛素敏感性及L细胞释放的GLP-1,并影响线粒体复合物I,活化十二指肠AMPK,以抑制肝糖异生及增加GLP-1水平,从而降低血糖;
并可通过调节菌群增强肠道屏障功能,增加短链脂肪酸水平,减少促炎症胆汁酸,抑制炎症延缓衰老。
延伸阅读

Pleiotropic effects of metformin: Shaping the microbiome to manage type 2 diabetes and postpone ageing

二甲双胍的多效性:塑造菌群以控制2型糖尿病并延缓衰老

2018-10-15, Review, 10.1016/j.arr.2018.10.003more

Abstract:
Metformin is the first-choice therapy to lower glycaemia and manage type 2 diabetes. Continuously emerging epidemiological data and experimental models are showing additional protective effects of metformin against a number of age-related diseases (ARDs), e.g., cardiovascular diseases and cancer. This evidence has prompted the design of a specific trial, i.e., the Targeting Aging with Metformin (TAME) trial, to test metformin as an anti-ageing molecule. However, a unifying or prevailing mechanism of action of metformin is still debated. Here, we summarize the epidemiological data linking metformin to ARD prevention. Then, we dissect the deeply studied mechanisms of action explaining its antihyperglycemic effect and the putative mechanisms supporting its anti-ageing properties, focusing on studies using clinically pertinent doses. We hypothesize that the molecular observations obtained in different models with metformin could be indirectly mediated by its effect on gut flora. Novel evidence suggests that metformin reshapes the human microbiota, promoting the growth of beneficial bacterial species and counteracting the expansion of detrimental bacterial species. In turn, this action would influence the balance between pro- and anti-inflammatory circulating factors, thereby promoting glycaemic control and healthy ageing. This framework may reconcile diverse observations, providing information for designing further studies to elucidate the complex interplay between metformin and the metabiome harboured in mammalian body compartments, thereby paving the way for innovative, bacterial-based therapeutics to manage type 2 diabetes and foster a longer healthspan.

First Authors:
Francesco Prattichizzo

Correspondence Authors:
Francesco Prattichizzo

All Authors:
Francesco Prattichizzo,Angelica Giuliani,Emanuela Mensà,Jacopo Sabbatinelli,Valeria De Nigris,Maria Rita Rippo,Lucia La Sala,Antonio Domenico Procopio,Fabiola Olivieri,Antonio Ceriello