Probiotics, Prebiotics, and Synbiotics Improve Uremic, Inflammatory, and Gastrointestinal Symptoms in End-Stage Renal Disease With Dialysis: A Network Meta-Analysis of Randomized Controlled Trials.

Background: Probiotics, prebiotics, and synbiotics are three different supplements to treat end stage renal disease (ESRD) patients by targeting gut bacteria. The comprehensive comparison of the effectiveness of different supplements are lacking. Objectives: The purpose of this network meta-analysis (NMA) is to assess and rank the efficacy of probiotics, prebiotics, and synbiotics on inflammatory factors, uremic toxins, and gastrointestinal symptoms (GI symptoms) in ESRD patients undergoing dialysis. Methods: Randomized clinical trials were searched from the PubMed, Embase, and Cochrane Register of Controlled Trials databases, from their inception until 4 September 2021. Random-effect model were used to obtain all estimated outcomes in network meta-analysis (NMA). Effect estimates were presented as mean differences (Mean ± SD) with 95% confidence interval (CI). The comprehensive effects of all treatments were ranked by the surface under the cumulative ranking (SUCRA) probabilities. Results: Twenty-five studies involved 1,106 participants were included. Prebiotics were superior in decreasing Interleukin-6 (IL-6; SMD -0.74, 95% CI [-1.32, -0.16]) and tumor-necrosis factor-α (TNF-α; SMD -0.59, 95% CI [-1.09, -0.08]), synbiotics were more effective in declining C-reactive protein (CRP; SMD -0.69, 95% CI [-1.14, -0.24]) and endotoxin (SMD -0.83, 95% CI [-1.38, -0.27]). Regarding uremic toxins, prebiotics ranked highest in reducing indoxyl sulfate (IS; SMD -0.43, 95% CI [-0.81, -0.05]), blood urea nitrogen (BUN; SMD -0.42, 95% CI [-0.78, -0.06]), and malondialdehyde (MDA; SMD -1.88, 95% CI [-3.02, -0.75]). Probiotics were rated as best in alleviating GI symptoms (SMD: -0.52, 95% CI [-0.93, -0.1]). Conclusion: Our research indicated prebiotics were more effective in declining IL-6, TNF-α, IS, MDA, and BUN, synbiotics lowering CRP and endotoxin significantly, and probiotics were beneficial for alleviating GI symptoms, which may contribute to better clinical decisions. This study was registered in PROSPERO (Number: CRD42021277056). Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42021277056].