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急性和慢性冠状动脉综合征对肠道微生物群及下游微生物衍生代谢产物的影响——急性心肌梗死中的微生物群——迈阿密试验

The influence of acute and chronic coronary syndrome on the gut microbiome and downstream microbiome-derived metabolites-Microbiome in acute myocardial infarction-MIAMI-Trial.

作者信息

Messiha Daniel, Lange Erik, Tratnik Annika, M Westendorf Astrid, Rinke Miriam, Lenz Stine, Hendgen-Cotta Ulrike B, Buer Jan, Rassaf Tienush, Rammos Christos

机构信息

Department of Cardiology and Vascular Medicine, West German Heart and Vascular Centre, University of Duisburg-Essen, Essen, Germany.

Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.

出版信息

Basic Res Cardiol. 2025 Aug 13. doi: 10.1007/s00395-025-01134-9.

Abstract

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the industrialized world. The gut microbiome influences CVD, through atherogenic metabolites like trimethylamine N-oxide (TMAO) or protective effects through short-chain fatty acids (SCFA) production. The specific alterations in the gut microbiome and downstream metabolites in acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) remain unclear. We enrolled ACS patients within 24 h of clinical presentation with a follow-up of 28 days, using CCS patients as controls. Gut microbiome composition, downstream metabolites, and cardiovascular function were assessed at both baseline and follow-up. Microbiome-derived metabolites were analyzed and gut microbiome samples were characterized by 16S rRNA gene analysis. We enrolled 40 patients, with 20 patients each in the ACS and CCS group. Alpha diversity of the microbiome did not differ throughout the follow-up. After ACS gut microbiome composition changed during the follow-up period with increased levels of Butyricicoccus and Butyricoccaceae, a pattern not observed in the CCS cohort. Downstream analysis of microbiome-derived metabolites SCFA revealed increased serum levels of butanoic acid, while TMAO levels remained unchanged. This small prospective observational non-randomized study, suggests that ACS may trigger an enrichment of butanoic acid-producing bacteria in the gut microbiome, accompanied by an increase in serum butanoic acid levels over 28 days. No significant changes in TMAO were observed. These insights could help develop approaches to reduce the burden of CVD. As a small pilot study, these findings require validation in larger ACS cohorts. Trial registration NCT, NCT05456802, Registered 30 June 2022, https://clinicaltrials.gov/study/NCT05122689.

摘要

心血管疾病(CVD)是工业化国家发病和死亡的主要原因。肠道微生物群通过三甲胺N-氧化物(TMAO)等致动脉粥样硬化代谢物或通过产生短链脂肪酸(SCFA)的保护作用来影响心血管疾病。急性冠状动脉综合征(ACS)和慢性冠状动脉综合征(CCS)中肠道微生物群和下游代谢物的具体变化仍不清楚。我们纳入了临床表现后24小时内的ACS患者,并随访28天,以CCS患者作为对照。在基线和随访时评估肠道微生物群组成、下游代谢物和心血管功能。分析微生物群衍生的代谢物,并通过16S rRNA基因分析对肠道微生物群样本进行表征。我们纳入了40名患者,ACS组和CCS组各20名。在整个随访过程中,微生物群的α多样性没有差异。ACS后,肠道微生物群组成在随访期间发生了变化,丁酸球菌属和丁酸球菌科的水平增加,这一模式在CCS队列中未观察到。对微生物群衍生的代谢物SCFA的下游分析显示,血清丁酸水平升高,而TMAO水平保持不变。这项小型前瞻性观察性非随机研究表明,ACS可能会引发肠道微生物群中产生丁酸的细菌富集,并伴随着28天内血清丁酸水平的升高。未观察到TMAO有显著变化。这些见解有助于开发减轻心血管疾病负担的方法。作为一项小型试点研究,这些发现需要在更大的ACS队列中进行验证。试验注册号NCT,NCT05456802,于2022年6月30日注册,https://clinicaltrials.gov/study/NCT05122689。

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