Impact of Gut Microbiome Modulation on Uremic Toxin Reduction in Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis

Abstract

Background/Objectives: Chronic kidney disease is associated with increased intestinal barrier permeability, leading to heightened inflammation and oxidative stress. These changes contribute to complications such as cardiovascular disease, anemia, altered mineral metabolism, and CKD progression. Interventions using prebiotics, probiotics, and synbiotics may mitigate dysbiosis and improve intestinal barrier function, Under this premise, the objective of this network meta-analysis was to evaluate the effect of probiotics, prebiotics, and synbiotics in reducing uremic toxins produced by the gut microbiota in CKD patients. Methods: A systematic review and network meta-analysis of randomized clinical trials (RCTs) was performed in the following databases: Web of Science, Scopus, the Cochrane Register of Controlled Trials, and PubMed published between 2019 and 2023. The analysis focused on the use of prebiotics, probiotics, and synbiotics in CKD patients at stages 3 to 5, as per KDIGO guidelines, and their association with reductions in uremic toxins such as Indoxyl Sulfate, p-Cresyl Sulfate, urea, and creatinine. The risk of bias was assessed using the Cochrane risk of bias tool (RoB 2), with evaluations conducted independently by two reviewers, and a third consulted for disagreements. The study follows the PRISMA statement. Results: The studies included 331 patients, primarily male, across CKD stages 3a to 5. The interventions positively impacted the gut microbiota composition, leading to reductions in free and total p-Cresyl Sulfate (SUCRA: 72.6% and 66.2, respectively) and indoxyl sulfate (SUCRA: 88.5% and 83.1%). Conclusions: The findings suggest that modulating the gut microbiota through these interventions can effectively reduce specific uremic toxins. However, further trials are necessary to better understand microbiota modulation and its impact on intestinal bacterial composition (PROSPERO number: CRD42023438901).