Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, China.
Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.
mSystems. 2023 Feb 23;8(1):e0130022. doi: 10.1128/msystems.01300-22. Epub 2023 Jan 23.
Metformin is a common drug for the management of type 2 diabetes mellitus; however, it causes various adverse gastrointestinal effects, especially after prolonged treatment. It is thus of interest to identify an adjuvant treatment that synergizes with the efficacy of metformin while mitigating its adverse effects. Since previous evidence supports that the gut microbiota is a target of metformin, this study investigated the beneficial effect and mechanism of the coadministration of probiotics with metformin in the management of type 2 diabetes mellitus by conducting a 3-month randomized, double-blind, placebo-controlled clinical trial ( = 27 and 21 in the probiotic and placebo groups, respectively, who completed the trial). Clinical results showed that the coadministration of probiotics with metformin significantly reduced glycated hemoglobin compared with metformin taken alone (0.05). Metagenomic and metabolomic analyses showed that the coadministration of probiotics increased the abundance of gut short-chain fatty acid (SCFA)-producing bacteria and bile acids. Significantly or marginally more bile acids and related metabolites were detected in the probiotic group than in the placebo group postintervention. Taken together, the results of our study showed that the coadministration of probiotics with metformin synergized with the hypoglycemic effect in patients with type 2 diabetes mellitus, which was likely through modulating the gut microbiome and, subsequently, SCFA and bile acid metabolism. Our findings support that cotreatment with probiotics and metformin is beneficial to patients with type 2 diabetes mellitus. Metformin causes variable adverse gastrointestinal effects, especially after prolonged treatment. We found that cotreatment with Probio-X and metformin for the management of type 2 diabetes mellitus may promote gut SCFA-producing bacteria and the levels of specific bile acids, thus increasing the secretion of related gastrointestinal hormones and ultimately improving glucose homeostasis.
二甲双胍是治疗 2 型糖尿病的常用药物；然而，它会引起各种胃肠道不良反应，尤其是在长期治疗后。因此，人们有兴趣寻找一种辅助治疗方法，既能增强二甲双胍的疗效，又能减轻其不良反应。由于先前有证据表明肠道微生物群是二甲双胍的作用靶点，因此本研究通过一项为期 3 个月的随机、双盲、安慰剂对照临床试验（分别有 27 名和 21 名益生菌组和安慰剂组患者完成了试验），调查了益生菌与二甲双胍联合用于 2 型糖尿病管理的有益效果和机制。临床结果表明，与单独使用二甲双胍相比，益生菌与二甲双胍联合使用可显著降低糖化血红蛋白（0.05）。宏基因组和代谢组学分析表明，与单独使用二甲双胍相比，益生菌联合使用可增加肠道短链脂肪酸（SCFA）产生菌和胆汁酸的丰度。干预后，益生菌组中检测到的胆汁酸和相关代谢物明显或略有增加。总的来说，我们的研究结果表明，益生菌与二甲双胍联合使用可协同增强 2 型糖尿病患者的降糖作用，这可能是通过调节肠道微生物群，进而调节 SCFA 和胆汁酸代谢实现的。我们的研究结果支持益生菌与二甲双胍联合治疗 2 型糖尿病患者是有益的。二甲双胍会引起不同的胃肠道不良反应，尤其是在长期治疗后。我们发现，益生菌与二甲双胍联合用于 2 型糖尿病的治疗可能会促进肠道产生 SCFA 的细菌和特定胆汁酸的水平，从而增加相关胃肠道激素的分泌，最终改善葡萄糖稳态。
