Institute of Healthy Ageing, and G.E.E., University College London, London WC1E 6BT, UK.
Cell. 2013 Mar 28;153(1):228-39. doi: 10.1016/j.cell.2013.02.035.
The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional and pathogenic effects on its nematode predator/host that impact health and aging. We report that metformin increases lifespan by altering microbial folate and methionine metabolism. Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic. Metformin increases or decreases worm lifespan, depending on E. coli strain metformin sensitivity and glucose concentration. In mammals, the intestinal microbiome influences host metabolism, including development of metabolic disease. Thus, metformin-induced alteration of microbial metabolism could contribute to therapeutic efficacy-and also to its side effects, which include folate deficiency and gastrointestinal upset.
双胍类药物二甲双胍被广泛用于治疗 2 型糖尿病和代谢综合征，但它的作用模式仍不确定。二甲双胍还可以延长与大肠杆菌共培养的秀丽隐杆线虫的寿命。这种细菌对其线虫捕食者/宿主施加复杂的营养和致病影响，从而影响健康和衰老。我们报告说，二甲双胍通过改变微生物叶酸和蛋氨酸代谢来延长寿命。通过突变线虫蛋氨酸合成酶（metr-1）和 S-腺苷甲硫氨酸合成酶（sams-1）改变二甲双胍诱导的寿命延长，表明二甲双胍在宿主中诱导蛋氨酸限制，这与该药物作为饮食限制模拟物的作用一致。二甲双胍可以增加或减少线虫的寿命，具体取决于大肠杆菌菌株对二甲双胍的敏感性和葡萄糖浓度。在哺乳动物中，肠道微生物组会影响宿主代谢，包括代谢疾病的发展。因此，二甲双胍诱导的微生物代谢改变可能有助于治疗效果，也可能导致其副作用，包括叶酸缺乏和胃肠道不适。
