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].