Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial
Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial
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DOI：
10.2215/cjn.05240515
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发表时间：
2016-02-01
影响因子：
9.8
通讯作者：
Campbell, Katrina L.
中科院分区：
文献类型：
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作者：
Rossi, Megan;Johnson, David W.;Campbell, Katrina L.
背景和目的：慢性肾脏病（CKD）患者肠道菌群失调导致了关键的尿毒症肾血管毒素硫酸吲哚酚（IS）和硫酸对甲苯酯（PCS）的产生。我们研究的目的是评估合生元是否（前和益生菌）治疗改变了CKD患者的肠道微生物群并降低了微生物群产生的尿毒症毒素IS和PCS的血清浓度。设计、设置、参与者和测量CKD成人参与者透析前在2013年1月5日至2013年11月12日期间，招募了10-30 ml/min（eGFR=10-30 ml/min/1.73 m2）的受试者，进行为期6周（4周洗脱期）的合生素治疗的随机、双盲、安慰剂对照、交叉试验。主要结果是血清IS。次要结局包括血清PCS、粪便微生物群特征、eGFR、蛋白尿-白蛋白尿、尿肾损伤分子-1、血清炎症生物标志物（IL-1 β、IL-6、IL-10和TNF-α）、血清氧化应激生物标志物（F-2-异前列腺素和谷胱甘肽过氧化物酶）、血清LPS、患者报告的健康状况、胃肠道症状评分和饮食摄入。结果在37名随机分组的受试者中（年龄=69 ± 10岁; 57%为男性; eGFR=24 ± 8 ml/min/1.73 m2），31人完成了研究。合生素治疗未显著降低血清IS（-2 μ mol/L; 95%置信区间[95% CI]，-5至1 μ mol/L），但显著降低血清PCS（-14 μ mol/L; 95% CI，-27至2 μ mol/L）。在研究期间未接受抗生素治疗的患者中，PCS和IS浓度的降低更为明显（n=21;血清PCS，-25 μ mol/L; 95% CI，-38至-12 μ mol/L;血清IS，-5 μ mol/L; 95% CI，-8至-1 μ mol/L）。合生元还改变了粪便微生物组，特别是双歧杆菌的富集和瘤胃球菌科的消耗。合生元组除白蛋白尿增加38 mg/24 h（P=0.03）外，其他次要结局均无变化。结论在CKD患者中，合生元并未显著降低血清IS，但降低了血清PCS，并有利地改善了粪便微生物组。大规模的临床试验是合理的。
Background and objectives The generation of key uremic nephrovascular toxins, indoxyl sulfate (IS), and p-cresyl sulfate (PCS), is attributed to the dysbiotic gut microbiota in CKD. The aim of our study was to evaluate whether synbiotic (pre- and probiotic) therapy alters the gut microbiota and reduces serum concentrations of microbiome-generated uremic toxins, IS and PCS, in patients with CKD.Design, setting, participants, & measurements Predialysis adult participants with CKD (eGFR=10-30 ml/min per 1.73 m(2)) were recruited between January 5, 2013 and November 12, 2013 to a randomized, double-blind, placebo-controlled, crossover trial of synbiotic therapy over 6 weeks (4-week washout). The primary outcome was serum IS. Secondary outcomes included serum PCS, stool microbiota profile, eGFR, proteinuria-albuminuria, urinary kidney injury molecule-1, serum inflammatory biomarkers (IL-1 beta, IL-6, IL-10, and TNF-alpha), serum oxidative stress biomarkers (F-2-isoprostanes and glutathione peroxidase), serum LPS, patient-reported health, Gastrointestinal Symptom Score, and dietary intake. A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect.Results Of 37 individuals randomized (age =69 +/- 10 years old; 57% men; eGFR=24 +/- 8 ml/min per 1.73 m(2)), 31 completed the study. Synbiotic therapy did not significantly reduce serum IS (-2 mu mol/L; 95% confidence interval [95% CI], -5 to 1 mu mol/L) but did significantly reduce serum PCS (-14 mu mol/L; 95% CI, -27 to -2 mu mol/L). Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study (n=21; serum PCS, -25 mu mol/L; 95% CI,-38 to-12 mu mol/L; serum IS, -5 mu mol/L; 95% CI,-8 to-1 mu mol/L). Synbiotics also altered the stool microbiome, particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae. Except for an increase in albuminuria of 38 mg/24 h (P=0.03) in the synbiotic arm, no changes were observed in the other secondary outcomes.Conclusion In patients with CKD, synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome. Large-scale clinical trials are justified.