Zhou Ruilin, Wu Qingyang, Qian Hao, Wang Liang, Liu Guangcheng, Zhang Bin, Wu Wei, Zhang Shuyang
Department of Cardiology Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China.
Eight-Year Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730 Beijing, China.
Rev Cardiovasc Med. 2025 May 27;26(5):26835. doi: 10.31083/RCM26835. eCollection 2025 May.
About 20% of patients with coronary artery disease (CAD) experience adverse events within five years of undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction. In these patients, the impact of metformin on long-term prognosis remains uncertain.
This study enrolled 22 metformin (Met)-CAD patients with diabetes mellitus (DM) who had been administered metformin for at least six months before PCI, 14 non-Met CAD-DM patients with DM who had never taken metformin or had stopped taking metformin for a year before PCI, and 22 matched healthy controls. A 5-year follow-up was conducted to collect clinical prognosis data. Fecal 16S rRNA sequencing and serum untargeted metabolomics analyses were performed. BugBase was utilized to analyze the possible functional changes in the gut microbiome. Multi-omics analysis was conducted using Spearman's correlation to explore the interactions between metformin, gut microbiome, serum metabolites, and clinical prognosis.
Metformin significantly lowered the 5-year major adverse cardiac events (MACEs) in Met CAD-DM patients. We found a higher abundance of , , , and in the Met CAD-DM patients, as well as an increase in hydroxy-alpha-sanshool (HAS) and decenoylcarnitine and a decrease in tridec-10-enoic acid, Z-vad-fmk (benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone), 3,9-dimethyluric acid in blood serum. Multi-omics analysis revealed that alterations in the gut microbiome and serum metabolites are significantly associated with the 5-year prognosis of CAD-DM.
Metformin significantly improved the 5-year prognosis of CAD patients following PCI. Metformin tended to have more positive effects on the commensal flora and metabolic profiles, which may explain its beneficial effects on cardiovascular health. This study revealed the potential associations between metformin and the gut microbiome, an associated alteration in serum metabolome, and the impact on the host immune system and metabolic pathways.
约20%的冠状动脉疾病（CAD）患者在接受经皮冠状动脉介入治疗（PCI）以治疗急性心肌梗死后五年内会发生不良事件。在这些患者中，二甲双胍对长期预后的影响仍不确定。
本研究纳入了22例在PCI前至少服用二甲双胍六个月的二甲双胍（Met）-CAD糖尿病（DM）患者、14例从未服用过二甲双胍或在PCI前一年已停止服用二甲双胍的非Met CAD-DM糖尿病患者，以及22例匹配的健康对照。进行了为期5年的随访以收集临床预后数据。进行了粪便16S rRNA测序和血清非靶向代谢组学分析。利用BugBase分析肠道微生物群可能的功能变化。使用Spearman相关性进行多组学分析，以探索二甲双胍、肠道微生物群、血清代谢物和临床预后之间的相互作用。
二甲双胍显著降低了Met CAD-DM患者的5年主要不良心脏事件（MACE）。我们发现Met CAD-DM患者中 、 、 和 的丰度较高，血清中羟基-α-山嵛醇（HAS）和癸酰肉碱增加，十三碳-10-烯酸、Z-VAD-FMK（苄氧羰基-Val-Ala-Asp（OMe）-氟甲基酮）、3,9-二甲基尿酸减少。多组学分析表明，肠道微生物群和血清代谢物的改变与CAD-DM的5年预后显著相关。
二甲双胍显著改善了PCI后CAD患者的5年预后。二甲双胍对共生菌群和代谢谱往往有更积极的影响，这可能解释了其对心血管健康的有益作用。本研究揭示了二甲双胍与肠道微生物群之间的潜在关联、血清代谢组的相关改变以及对宿主免疫系统和代谢途径的影响。
