(OR06-02-25) Dietary Fiber Fermentability and Viscosity Impact Serum and Gut Microbial Metabolites in a Rat Model of Progressive Chronic Kidney Disease (CKD)

Objectives: Dietary fiber modulates microbial metabolism, possibly impacting CKD pathogenesis and complications. However, there is limited data on how dietary fiber’s properties shape these effects. We hypothesized that dietary fiber differentially impacts serum and gut microbial metabolites based on their fermentability and viscosity properties in a rat model of progressive CKD.

Methods: 22-wk-old Cy/+ male rats were randomly assigned to one of four fiber treatments, all 10% w/w: 1) Cellulose (non-viscous, non-fermentable; negative control), 2) Inulin (non-viscous, fermentable), 3) Psyllium (viscous, non-fermentable), or 4) Pectin (viscous, fermentable). Treatments lasted 11 weeks and rats were euthanized at 33 wks of age (kidney failure; ~15% of normal). Targeted metabolomic analysis was conducted to quantify serum and cecum microbial metabolites, including uremic toxins (trimethylamine-N-oxide [TMAO], indoxyl sulfate [IS], p-cresyl sulfate [PCS]), short-chain fatty acids (SCFA), and other tryptophan-derived metabolites (indole-3-acetic acid [IAA], indole-3-lactic acid [ILA], indole-3-propionic acid [IPA]. Statistical comparisons were performed using one-way ANOVA with Tukey’s post hoc p-correction and significance set as p≤0.05.

Results: Compared to cellulose, inulin-treated rats had lower serum TMAO levels, while inulin and psyllium had lower IS and PCS. Regarding SCFA, compared to all other treatments, cecum and serum acetate concentrations were higher with pectin, cecum propionate was higher with inulin compared to psyllium, while cecum and serum butyrate was higher with inulin compared to cellulose. Serum IAA levels were higher with inulin and psyllium, while pectin and psyllium increased serum IPA levels compared to cellulose. Finally, compared to cellulose, cecal IAA levels were lower with inulin and pectin, ILA was higher with inulin, and IPA was higher with pectin.

Conclusions: Fermentable and viscous fibers differentially impacted microbially-derived uremic toxins, SCFA, and tryptophan metabolites in a rat model of CKD, suggesting that dietary fiber based on its physicochemical properties may serve as a promising strategy for modulating gut-derived metabolites in CKD management.

Funding Sources: K1K12 TR004415, KL2TR002530, UL1TR002529, Showalter Trust, and Purdue AgSEED