Dietary fiber reduces indoxyl sulfate by 0.13 mg/dL in humans with CKDDietary Fiber May Lower Harmful Gut Metabolites in Kidney Disease

Background: Chronic kidney disease (CKD) is associated with alterations in the gut microbiome that promote the accumulation of gut-derived uremic solutes and contribute to systemic inflammation, vascular dysfunction, and disease progression. Dietary fiber has emerged as a promising modulator of gut microbial metabolism, yet the influence of fiber physicochemical properties, particularly fermentability and viscosity, on uremic metabolite production in CKD remains poorly understood. Objective: To systematically evaluate the effects of isolated dietary fiber interventions, classified by fermentability and viscosity, on gut microbial metabolites in CKD across experimental rodent models and randomized clinical trials, and to determine whether these fiber properties modify microbial metabolites. Methods: A systematic search of PubMed, Embase, CINAHL, and Cochrane Library (through June 2026) identified randomized controlled trials and controlled rodent studies assessing isolated dietary fiber in CKD. Eligible studies reported at least one gut-derived metabolite (i.e., indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine-N-oxide (TMAO), tryptophan-derived indoles, or short-chain fatty acids (SCFAs)). Random-effects models were used for pooled estimates using weighted mean differences (WMD) for human studies and standardized mean differences (SMD) for animal studies. Subgroup analyses evaluated fiber fermentability, viscosity, intervention dose, duration, and CKD stage. Risk of bias was assessed with ROB-2 and SYRCLE, and evidence certainty with GRADE. Results: Twenty-eight studies (13 human, 15 animal) met eligibility criteria, comprising 511 participants and 312 animals with CKD. Isolated fiber supplementation, primarily fermentable and non-viscous fibers, reduced IS (human: -0.13 mg/dL; 95% CI: -0.25, -0.01; p = 0.03; animal: -1.99; 95% CI: -3.06, -0.92; p < 0.0001) and pCS (human: -0.23 mg/dL; 95% CI: -0.46, 0.001; p = 0.051; animal: -1.56; 95% CI: -2.08, -1.03; p < 0.0001). SCFAs increased in animal studies, including cecal acetate (2.00, 95% CI: 0.78 to 3.22; p = 0.001) and circulating propionate (1.51, 95% CI: 0.054 to 2.96; p=0.04). There were no dose-dependent effects, but longer interventions (>8 weeks) tended to lower pCS (-0.26 mg/dL, 95% CI: -0.55 to 0.02; p=0.06). Some heterogeneity and low-to-moderate certainty were observed. Conclusion: Isolated dietary fiber reduces major gut-derived uremic solutes in CKD, with fermentability influencing metabolic responsiveness, but with minimal studies on viscous fibers. Larger, longer-duration trials with standardized reporting of total fiber intake and clinical endpoints are needed to guide evidence-based dietary recommendations in CKD.