Xi yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Peking University Traditional Chinese Medicine Clinical Medical School (Xi yuan), Beijing, China.
Adv Nutr. 2022 Aug 1;13(4):1267-1278. doi: 10.1093/advances/nmab149.
Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, exacerbate the deterioration of renal function and increase the risk of cardiovascular events in chronic kidney disease (CKD) patients. The effects of microbiota-driven therapy (probiotics, prebiotics, or synbiotics) on decreasing circulating IS and PCS concentrations are controversial; thus, we performed the present systematic review and meta-analysis to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients. PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to 22 July, 2021, and randomized controlled trials (RCTs) investigating the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients were included. In all, 14 RCTs with 513 participants were eligible for the meta-analysis. The effects of microbiota-driven therapy on the circulating IS and PCS concentrations were evaluated with weighted mean differences (WMDs) measured by a fixed-effects model or a random-effects model. Compared with placebo, microbiota-driven therapy had no statistically significant effect on the circulating IS concentration (WMD: -1.64 mg/L; 95% CI: -3.46, 0.18 mg/L; P = 0.077) but it decreased the circulating PCS concentration (WMD: -2.42 mg/L; 95% CI: -3.81, -1.04 mg/L; P = 0.001). In the subgroup analyses, prebiotic (n = 6) and synbiotic (n = 3) supplementation significantly decreased the circulating PCS concentration, whereas probiotic (n = 3) supplementation did not. Meta-regression showed that the effects of microbiota-driven therapy were not associated with the supplementation time or the year of publication. Moreover, there was no significant evidence of publication bias. This review found that microbiota-driven therapy decreased the circulating PCS concentration in CKD patients. Additional large, well-designed RCTs with improved methodology and reporting are necessary to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in the long term. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42021269146.
硫酸吲哚酚（IS）和对甲酚硫酸酯（PCS）是蛋白结合型尿毒症毒素，可加重慢性肾脏病（CKD）患者肾功能恶化，并增加心血管事件风险。微生物群驱动治疗（益生菌、益生元或合生元）对降低循环 IS 和 PCS 浓度的影响存在争议；因此，我们进行了本次系统评价和荟萃分析，以评估微生物群驱动治疗对 CKD 患者循环 IS 和 PCS 浓度的影响。我们系统地检索了 PubMed、EMBASE 和 Cochrane Library 数据库，检索时间从建库至 2021 年 7 月 22 日，并纳入了研究微生物群驱动治疗对 CKD 患者循环 IS 和 PCS 浓度影响的随机对照试验（RCT）。共有 14 项 RCT 纳入 513 名患者，符合荟萃分析条件。采用固定效应模型或随机效应模型，通过加权均数差（WMD）评估微生物群驱动治疗对循环 IS 和 PCS 浓度的影响。与安慰剂相比，微生物群驱动治疗对循环 IS 浓度无统计学意义的影响（WMD：-1.64mg/L；95%CI：-3.46，0.18mg/L；P=0.077），但降低了循环 PCS 浓度（WMD：-2.42mg/L；95%CI：-3.81，-1.04mg/L；P=0.001）。亚组分析显示，益生元（n=6）和合生元（n=3）补充剂可显著降低循环 PCS 浓度，而益生菌（n=3）补充剂则无此作用。Meta 回归显示，微生物群驱动治疗的效果与补充时间或发表年份无关。此外，不存在明显的发表偏倚。本综述发现，微生物群驱动治疗可降低 CKD 患者的循环 PCS 浓度。需要更多设计合理、方法改进、报告全面的大型 RCT 来评估微生物群驱动治疗对循环 IS 和 PCS 浓度的长期影响。本系统评价已在 www.crd.york.ac.uk/prospero/ 上注册，注册号为 CRD42021269146。
