(P40-18-26) Dietary Fiber Fermentability and Viscosity Influence Gut Microbial Metabolites in Chronic Kidney Disease: A Systematic Review and Meta Analysis of Animal and Clinical Trials

Objectives: To systematically evaluate the effects of isolated dietary fiber interventions on microbially-derived metabolites in chronic kidney disease (CKD), and to determine whether fiber fermentability and viscosity modify metabolite responses across both human trials and animal models.

Methods: A systematic review and meta-analysis of randomized controlled trials and animal studies was conducted searching PubMed, Embase, Web of Science, and CENTRAL (search through 02/06/2026). Eligible studies reported ≥1 gut-derived metabolite, including 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, and subgroup analyses evaluated fiber fermentability, viscosity, dose ( < 16 vs ≥16 g/day), intervention duration (≤8 vs >8 weeks), and CKD stage. Risk of bias (ROB-2, SYRCLE) and certainty (GRADE) were assessed.

Results: Twenty-eight studies (13 human, 15 animal) were included, comprising 511 participants and 312 animals with CKD. Across models, 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)). Further, there were no dose-dependent effects (p >0.05), 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.

Conclusions: This is the first systematic review and meta-analysis of both human and animal models in CKD examining the effects of isolated dietary fiber on gut-derived uremic toxins. Our results demonstrate that fermentability is a key determinant of metabolic effects, but that there is minimal work exploring viscous fibers. These findings highlight a mechanistic rationale for greater consideration of functional characteristics of fiber in dietary guidance.

Funding Sources: Indiana CTSI KL2/K12