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Abstract: TH-PO810

The Dietary Fiber Inulin Beneficially Alters the Gut Microbiota and Microbially-Derived Metabolites in a Rat Model of Progressive CKD

Session Information

Category: Health Maintenance‚ Nutrition‚ and Metabolism

  • 1400 Health Maintenance‚ Nutrition‚ and Metabolism

Authors

  • Biruete, Annabel, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Srinivasan, Shruthi, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • O'Neill, Kalisha, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • De loor, Henriette, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Evenepoel, Pieter, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Swanson, Kelly, University of Illinois Urbana-Champaign, Urbana, Illinois, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Inulin is a fermentable dietary fiber that may be able to 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 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 10 weeks (until the CKD animals had a GFR ~ 15% or normal) to test the hypothesis that fiber type affects the cecal microbiota and derived metabolites, including uremic toxins. 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

There was no difference in CKD progression in the CKD animals with the two types of fiber. The a-diversity, or diversity within a sample, was lower with CKD+IN treatment across different metrics (p<0.03) than CKD+CE and NL. B-diversity, or diversity between samples, was also different in CKD+IN vs. CKD+CE or NL (PERMANOVA q=0.03). 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 (p<0.0008) to concentrations similar to the NL rats despite no difference in kidney function between CKD+CE and CKD+IN.

Conclusion

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, including butyrate and uremic toxins. This suggests that adequate dietary fiber substrates can improve uremic dysbiosis and reduce toxin production.

Funding

  • NIDDK Support