|Title:||The dietary fiber inulin beneficially alters the gut microbiota and microbially-derived metabolites in a rat model of progressive CKD|
Biruete, Annabel, Purdue University; Shruthi Srinivasan, Indiana University School of Medicine; Kalisha O’Neill, Indiana University School of Medicine; Henriette de Loor, Katholieke Universiteit Leuven; Pieter Evenepoel, Katholieke Universiteit Leuven; Kelly Swanson, University of Illinois at Urbana-Champaign; Neal X. Chen, Indiana University School of Medicine; Sharon M. Moe, Indiana University School of Medicine
Background/Significance/Rationale: Inulin is a fermentable dietary fiber that may improve uremic dysbiosis. Our objective was to evaluate if inulin impacts the gut microbiota and derived metabolites in a rat model of CKD-MBD.
Methods: The male Cy/+ rats, a model of progressive CKD, were fed a grain-based diet until 22 weeks of age and then changed to a casein-based diet with either inulin (CKD+IN) or cellulose (non-fermentable fiber; CKD+CE) for 8 weeks (until the CKD animals had a GFR ~ 15% of normal) to test the hypothesis that fiber type affects the cecal microbiota and derived metabolites. NL littermates were treated with a casein-based diet with cellulose (NL). Cecal microbiota, cecal and serum butyrate, and microbially-derived serum uremic toxins were analyzed.
Results/Findings: There was no difference in CKD progression in the CKD animals with the two types of fiber. The -diversity, or diversity within a sample, was lower with CKD+IN treatment across different metrics than CKD+CE and NL. B-diversity, or diversity between samples, was also different in CKD+IN vs. CKD+CE or NL At the genera-level, CKD+IN (vs. CKD+CE or NL) had a higher relative abundance of Allobacullum, Bacteroides, Parabacteroides, Bifidobacterium, and Sutterella, and lower Clostridium, unclassified Peptostreptococcaceae, U. Desulfovibrionaceae, U. Ruminococcaceae, and Oscillospira (p<0.05). Fecal and serum butyrate, a short-chain fatty acid produced by the microbiota, were increased in the CKD+IN by 3- and 7-fold, respectively, vs. NL and CKD+CE (p<0.03). CKD+IN lowered the elevated levels of indoxyl sulfate and p-cresyl sulfate found in the CKD+CE group to concentrations similar to the NL rats despite no difference in kidney function between CKD+CE and CKD+IN.
Conclusions/Discussion: In our rat model of CKD-MBD, the fermentable fiber inulin, compared to non-fermentable fiber cellulose, improved the gut microbiota composition and the microbially-derived metabolites.
Translational/Human Health Impact: Our results suggest that adequate dietary fiber substrates can improve uremic dysbiosis and reduce toxin production.