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

Background: There is accumulating evidence that modification of the microbiota through prebiotic, probiotic or synbiotic supplementation in individuals with end-stage renal disease receiving dialysis may be efficacious in reducing circulating levels of toxic metabolites. This systematic review and meta-analyses provides 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. Randomised controlled trials of adult end stage renal-disease individuals receiving either haemodialysis 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 sulphate. Results: Twenty-one trials were eligible (1152 randomised 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. Synthesised data indicated that supplementation significantly reduced circulating levels of endotoxin (standardised mean difference -0.61, 95% confidence interval -1.03 to -0.20, P=0.004, I 2 =0%), indoxyl-sulphate (-0.34, -0.64 to -0.04, P=0.02, I2 =0%) and p-cresyl sulphate (-0.34, -0.61 to -0.07, P=0.01, I2 =0%). For secondary outcomes supplementation significantly reduced gastrointestinal symptoms (-0.54, -1.02 to -0.07, P=0.02, I2 =0%). Conclusions: Supplementation reduces toxic metabolites associated with cardiovascular disease and mortality in individuals receiving dialysis. However, the majority of trials included in quality.