Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.
Neuroscience Institute, Georgia State University, Atlanta, Georgia.
Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E1121-E1130. doi: 10.1152/ajpendo.00245.2019. Epub 2019 Oct 1.
Metformin beneficially impacts several aspects of metabolic syndrome including dysglycemia, obesity, and liver dysfunction, thus making it a widely used frontline treatment for early-stage type 2 diabetes, which is associated with these disorders. Several mechanisms of action for metformin have been proposed, including that it acts as an anti-inflammatory agent, possibly as a result of its impact on intestinal microbiota. In accord with this possibility, we observed herein that, in mice with diet-induced metabolic syndrome, metformin impacts the gut microbiota by preventing its encroachment upon the host, a feature of metabolic syndrome in mice and humans. However, the ability of metformin to beneficially impact metabolic syndrome in mice was not markedly altered by reduction or elimination of gut microbiota, achieved by the use of antibiotics or germfree mice. Although reducing or eliminating microbiota by itself suppressed diet-induced dysglycemia, other features of metabolic syndrome including obesity, hepatic steatosis, and low-grade inflammation remained suppressed by metformin in the presence or absence of gut microbiota. These results support a role for anti-inflammatory activity of metformin, irrespective of gut microbiota, in driving some of the beneficial impacts of this drug on metabolic syndrome.
二甲双胍对代谢综合征的多个方面有益，包括血糖异常、肥胖和肝功能障碍，因此它被广泛用于治疗与这些疾病相关的早期 2 型糖尿病。二甲双胍的作用机制有多种，包括它作为一种抗炎药物的作用，可能是由于它对肠道微生物群的影响。根据这一可能性，我们在此观察到，在饮食诱导代谢综合征的小鼠中，二甲双胍通过阻止其侵犯宿主来影响肠道微生物群，这是小鼠和人类代谢综合征的一个特征。然而，通过使用抗生素或无菌小鼠来减少或消除肠道微生物群，并没有显著改变二甲双胍对小鼠代谢综合征的有益影响。虽然单独减少或消除微生物群本身可抑制饮食诱导的血糖异常，但在存在或不存在肠道微生物群的情况下，肥胖、肝脂肪变性和低度炎症等代谢综合征的其他特征仍被二甲双胍抑制。这些结果支持二甲双胍的抗炎活性作用，无论是否存在肠道微生物群，在驱动这种药物对代谢综合征的一些有益影响方面发挥作用。
