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心力衰竭与肠道核心微生物群的耗竭有关。

Heart failure is associated with depletion of core intestinal microbiota.

作者信息

Luedde Mark, Winkler Thorben, Heinsen Femke-Anouska, Rühlemann Malte C, Spehlmann Martina E, Bajrovic Amer, Lieb Wolfgang, Franke Andre, Ott Stephan J, Frey Norbert

机构信息

Department of Internal Medicine III (Cardiology, Angiology and Intensive Care Medicine), University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.

DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Kiel, Germany.

出版信息

ESC Heart Fail. 2017 Aug;4(3):282-290. doi: 10.1002/ehf2.12155. Epub 2017 Apr 21.

Abstract

AIMS

In spite of current medical treatment approaches, mortality of chronic heart failure (HF) remains high and novel treatment modalities are thus urgently needed. A recent theory proposes a possible impact of the intestinal microbiome on the incidence and clinical course of heart failure. This study sought to systematically investigate, if there are specific changes of the intestinal microbiome in heart failure patients.

METHODS AND RESULTS

The intestinal microbiome of 20 patients with heart failure with reduced ejection fraction due to ischemic or dilated cardiomyopathy was investigated by applying high-throughput sequencing of the bacterial 16S rRNA gene. Microbial profiles were compared to those of matched controls in which heart failure was ruled out by clinical assessment and NT-proBNP serum levels (n = 20). According to the Shannon diversity index (which measures the intra-individual alpha-diversity) based on the distribution of operational taxonomic units (OTUs), HF cases showed a nominally significantly lower diversity index compared to controls (P  = 0.01), and testing for genera abundance showed a tendency towards a decreased alpha diversity of HF patients. Beta-diversity measures (inter-individual diversity) revealed a highly significant separation of HF cases and controls, (e.g. P  = 0.004). Assessing the individual abundance of core measurable microbiota (CMM), a significant decrease of Coriobacteriaceae, Erysipelotrichaceae and Ruminococcaceae was observed on the family level. In line with that, Blautia, Collinsella, uncl. Erysipelotrichaceae and uncl. Ruminococcaceae showed a significant decrease in HF cases compared to controls on the genus level.

CONCLUSIONS

Heart failure patients showed a significantly decreased diversity of the intestinal microbiome as well as a downregulation of key intestinal bacterial groups. Our data point to an altered intestinal microbiome as a potential player in the pathogenesis and progression of heart failure.

摘要

目的

尽管有当前的医学治疗方法,但慢性心力衰竭(HF)的死亡率仍然很高,因此迫切需要新的治疗方式。最近的一种理论提出肠道微生物群可能对心力衰竭的发病率和临床病程有影响。本研究旨在系统调查心力衰竭患者的肠道微生物群是否存在特定变化。

方法与结果

通过对细菌16S rRNA基因进行高通量测序,研究了20例因缺血性或扩张型心肌病导致射血分数降低的心力衰竭患者的肠道微生物群。将微生物谱与匹配的对照组进行比较,对照组通过临床评估和NT-proBNP血清水平排除了心力衰竭(n = 20)。根据基于操作分类单元(OTU)分布的香农多样性指数(衡量个体内α多样性),与对照组相比,HF病例的多样性指数名义上显著降低(P = 0.01),对属丰度的测试显示HF患者的α多样性有降低趋势。β多样性测量(个体间多样性)显示HF病例和对照组有高度显著的分离(例如P = 0.004)。评估核心可测量微生物群(CMM)的个体丰度,在科水平上观察到双歧杆菌科、丹毒丝菌科和瘤胃球菌科显著减少。与此一致,在属水平上,与对照组相比,HF病例中的布劳特氏菌属、柯林斯菌属、未分类的丹毒丝菌科和未分类的瘤胃球菌科显著减少。

结论

心力衰竭患者的肠道微生物群多样性显著降低,关键肠道细菌群也下调。我们的数据表明肠道微生物群的改变可能是心力衰竭发病机制和进展中的一个潜在因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/680f/5747045/2e7cd87ba249/EHF2-4-282-g001.jpg

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