利福昔明或布拉氏酵母菌在射血分数降低的心力衰竭中的作用：随机 GutHeart 试验的结果。
Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial.
机构信息
Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0450 Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0450 Oslo, Norway; Department of Cardiology, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
出版信息
EBioMedicine. 2021 Aug;70:103511. doi: 10.1016/j.ebiom.2021.103511. Epub 2021 Jul 28.
BACKGROUND
The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF).
METHODS
In a multicentre, prospective randomized open label, blinded end-point trial, we randomized patients with LVEF <40% and New York Heart Association functional class II or III, despite optimal medical therapy, to treatment (1:1:1) with the probiotic yeast Saccharomyces boulardii, the antibiotic rifaximin, or standard of care (SoC) only. The primary endpoint, the baseline-adjusted LVEF at three months, was assessed in an intention-to-treat analysis.
FINDINGS
We enrolled a total of 151 patients. After three months' treatment, the LVEF did not differ significantly between the SoC arm and the rifaximin arm (mean difference was -1•2 percentage points; 95% CI -3•2 - 0•7; p=0•22) or between the SoC arm and the Saccharomyces boulardii arm (mean difference -0•2 percentage points; 95% CI -2•2 - 1•9; p=0•87). We observed no significant between-group differences in changes in microbiota diversity, TMAO, or C-reactive protein.
INTERPRETATION
Three months' treatment with Saccharomyces boulardii or rifaximin on top of SoC had no significant effect on LVEF, microbiota diversity, or the measured biomarkers in our population with HF.
FUNDING
The trial was funded by the Norwegian Association for Public Health, the Blix foundation, Stein Erik Hagen's Foundation for Clinical Heart Research, Ada og Hagbart Waages humanitære og veldedige stiftelse, Alfasigma, and Biocodex.
背景
肠道微生物群代表了心力衰竭（HF）治疗的一个潜在靶点，通过微生物代谢产物，如三甲胺 N-氧化物（TMAO）和全身炎症。益生菌酵母布拉氏酵母菌的治疗已被建议改善左心室射血分数（LVEF）。
方法
在一项多中心、前瞻性随机开放标签、盲终点试验中，我们将 LVEF<40%和纽约心脏协会功能 II 或 III 级的患者，尽管接受了最佳的药物治疗，随机分为益生菌酵母布拉氏酵母菌、抗生素利福昔明或标准治疗（SoC）治疗组（1:1:1）。主要终点为三个月时的基线调整 LVEF，采用意向治疗分析进行评估。
结果
我们共纳入了 151 名患者。经过三个月的治疗，SoC 组与利福昔明组的 LVEF 差异无统计学意义（平均差异为-1•2 个百分点；95%CI -3•2 - 0•7；p=0•22），SoC 组与布拉氏酵母菌组的 LVEF 差异也无统计学意义（平均差异-0•2 个百分点；95%CI -2•2 - 1•9；p=0•87）。我们未观察到菌群多样性、TMAO 或 C 反应蛋白的组间变化有显著差异。
结论
在 SoC 的基础上加用布拉氏酵母菌或利福昔明治疗三个月，对我们 HF 患者的 LVEF、菌群多样性或所测生物标志物均无显著影响。
资助
该试验由挪威公共卫生协会、Blix 基金会、Stein Erik Hagen 临床心脏研究基金会、Ada og Hagbart Waages 人文与慈善基金会、Alfasigma 和 Biocodex 资助。
Zotero 插件