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肠道微生物组和血浆微生物组相关代谢物在失代偿性和代偿性心力衰竭患者中的变化。

Gut Microbiome and Plasma Microbiome-Related Metabolites in Patients With Decompensated and Compensated Heart Failure.

机构信息

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine.

School of Life Science and Technology, Tokyo Institute of Technology.

出版信息

Circ J. 2018 Dec 25;83(1):182-192. doi: 10.1253/circj.CJ-18-0468. Epub 2018 Nov 29.

Abstract

BACKGROUND

Gut microbiome composition or circulating microbiome-related metabolites in patients with heart failure (HF) have not been investigated at different time points (i.e., in the decompensated (Decomp) and compensated (Comp) phases).

METHODS AND RESULTS

We prospectively enrolled 22 patients admitted for HF and 11 age-, sex-, and comorbidity-matched hospitalized control subjects without a history of HF. Gut flora and plasma microbiome-related metabolites were evaluated by amplicon sequencing of the bacterial 16S ribosomal RNA gene and capillary electrophoresis time-of-flight mass spectrometry, respectively. HF patients were evaluated in both the Decomp and Comp phases during hospitalization. The phylum Actinobacteria was enriched in HF patients compared with control subjects. At the genus level, Bifiodobacterium was abundant while Megamonas was depleted in HF patients. Meanwhile, plasma concentration of trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, was increased in HF patients (Decomp HF vs. control, P=0.003; Comp HF vs. control, P=0.004). A correlation analysis revealed positive correlations between the abundance of the genus Escherichia/Shigella and levels of TMAO and indoxyl sulfate (IS, a microbe-dependent uremic toxin) in Comp HF (TMAO: r=0.62, P=0.002; IS: r=0.63, P=0.002). Escherichia/Shigella was more abundant in Decomp than in Comp HF (P=0.030).

CONCLUSIONS

Our results suggest that gut microbiome composition and microbiome-related metabolites are altered in HF patients.

摘要

背景

尚未在不同时间点(即失代偿期(Decomp)和代偿期(Comp))对心力衰竭(HF)患者的肠道微生物组组成或循环微生物组相关代谢物进行研究。

方法和结果

我们前瞻性地招募了 22 名因 HF 入院的患者和 11 名年龄、性别和合并症相匹配的无 HF 病史的住院对照患者。通过细菌 16S 核糖体 RNA 基因扩增子测序和毛细管电泳飞行时间质谱法分别评估肠道菌群和血浆微生物组相关代谢物。HF 患者在住院期间分别处于 Decomp 和 Comp 阶段进行评估。与对照相比,厚壁菌门在 HF 患者中丰富。在属水平上,双歧杆菌丰富,而 Megamonas 在 HF 患者中耗尽。同时,HF 患者的血浆三甲胺 N-氧化物(TMAO)浓度增加,这是一种肠道微生物组衍生的代谢物(Decomp HF 与对照相比,P=0.003;Comp HF 与对照相比,P=0.004)。相关性分析显示,Comp HF 中属埃希氏菌/志贺氏菌的丰度与 TMAO 和吲哚硫酸(IS,一种依赖微生物的尿毒症毒素)的水平呈正相关(TMAO:r=0.62,P=0.002;IS:r=0.63,P=0.002)。与 Comp HF 相比,Decomp HF 中埃希氏菌/志贺氏菌更为丰富(P=0.030)。

结论

我们的结果表明,HF 患者的肠道微生物组组成和微生物组相关代谢物发生了改变。

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