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共生元治疗对慢性肾脏病患者肠道来源尿毒症毒素、炎症和肠道微生物组水平的影响:一项随机试验。

The Impact of Synbiotic Treatment on the Levels of Gut-Derived Uremic Toxins, Inflammation, and Gut Microbiome of Chronic Kidney Disease Patients-A Randomized Trial.

机构信息

Clinical Department for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia.

Nephrology Clinic, Clinical Center Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Belgrade, Serbia.

出版信息

J Ren Nutr. 2023 Mar;33(2):278-288. doi: 10.1053/j.jrn.2022.07.008. Epub 2022 Aug 19.

Abstract

OBJECTIVE

Altering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.

METHODS

A total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.

RESULTS

Synbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS -21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (-39.5 vs. -8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.

CONCLUSION

Synbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.

摘要

目的

通过共生元补充来改变失调的肠道菌群,最近已被认为是一种潜在的治疗策略,可以降低肠道来源的尿毒症毒素水平并减少炎症。评估其疗效和安全性一直是我们这项随机、双盲、安慰剂对照研究的主要目标。

方法

共有 34 名年龄≥18 岁的非透析慢性肾脏病患者,肾小球滤过率估计值在 15 至 45ml/min 之间,被随机分为干预组(n=17),接受共生元(嗜酸乳杆菌、干酪乳杆菌和双歧杆菌,每天 320 亿个菌落形成单位加 3.2g 菊粉)或对照组(n=17),在 12 周内接受安慰剂。治疗对肠道来源的尿毒症毒素、总血清吲哚硫酸、对甲酚硫酸和三甲胺 N-氧化物的动态变化的影响被定义为研究的主要结果。次要结果包括粪便微生物组、血清白细胞介素-6 水平、高敏 C 反应蛋白、肾小球滤过率估计值、蛋白尿、饮食、胃肠道症状动态和安全性的变化。使用超高效液相色谱法测定尿毒症毒素的血清水平。使用 16S 核糖体 RNA 基因测序方法进行粪便微生物组分析。

结果

共生元治疗显著改变了肠道微生物组,双歧杆菌、乳杆菌和 Subdoligranulum 属的丰度增加,随后降低了吲哚硫酸的血清水平(ΔIS-21.5%对 5.3%,P<0.001),改善了肾小球滤过率估计值(ΔeGFR 12%对 8%,P=0.029),降低了高敏 C 反应蛋白水平(-39.5%对-8.5%,P<0.001)。干预组有 2 名患者抱怨腹胀增加。没有其他安全问题。

结论

共生元可能是一种有效的治疗策略,在日常实践中,我们可以使用它来降低慢性肾脏病患者的尿毒症毒素和微炎症水平。

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