Effects of Microbiota-Driven Therapy on Circulating Indoxyl Sulfate and P-Cresyl Sulfate in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

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 the circulating IS and PCS concentrations in CKD patients. PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to July 22, 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, the 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: –2.44 mg/L; 95% CI: –3.82, –1.05 mg/L; P = 0.001). In the subgroup analyses, prebiotic (n = 5) and synbiotic (n = 3) supplementation significantly decreased the circulating PCS concentration, while probiotic (n = 4) 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, randomized controlled trials with improved methodology and reporting are necessary to assess the effects of microbiota-driven therapy on the circulating IS and PCS concentrations in the long term. Significance: The findings of clinical studies investigating the effects of microbiota-driven therapy on the reduction of IS and PCS concentrations in CKD patients are controversial. To the best of our knowledge, this is the first study to systematically assesses the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients.

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