The efficacy of prebiotic, probiotic and synbiotic supplementation in modulating gut-derived circulatory particles associated with cardiovascular disease in individuals receiving dialysis: a systematic review and meta-analysis of randomized controlled trials

Objective
This systematic review and meta-analyses provide an up-to-date synthesis on the effects of supplementation on circulating levels of toxic metabolites, markers of uremia and inflammation, blood lipids, and other clinical outcomes.

Methods
Seventeen databases were searched, supplemented with internet and hand searching. Randomized controlled trials of adult end-stage renal-disease individuals receiving either hemodialysis or peritoneal dialysis were eligible. Trials were restricted to those which had administered a prebiotic, probiotic, or synbiotic as an oral supplement. Primary outcomes were measures of circulating endotoxin, indoxyl-sulphate, and p-cresyl sulfate.

Results
Twenty-one trials were eligible (1152 randomized participants), of which 16 trials were considered to have a high risk of bias. The number of trials available for meta-analysis varied for each primary outcome. Synthesized data indicated that supplementation significantly reduced circulating levels of endotoxin (standardized mean difference, −0.61; 95% confidence interval, −1.03 to −0.20; P = .004; I2 = 0%), indoxyl-sulphate (−0.34; −0.64 to −0.04; P = .02; I2 = 0%), and p-cresyl sulfate (−0.34; −0.61 to −0.07; P = .01; I2 = 0%). For secondary outcomes, supplementation significantly reduced gastrointestinal symptoms (−0.54; −1.02 to −0.07; P = .02; I2 = 0%).

Conclusions
Supplementation reduces toxic metabolites associated with cardiovascular disease and mortality in individuals receiving dialysis. However, the majority of trials included were low in quality.