Resistant starch slows the progression of CKD in the 5/6 nephrectomy mouse model

Physiol Rep. 2020 Oct;8(19):e14610. doi: 10.14814/phy2.14610.


Background: Resistant Starch (RS) improves CKD outcomes. In this report, we study how RS modulates host-microbiome interactions in CKD by measuring changes in the abundance of proteins and bacteria in the gut. In addition, we demonstrate RS-mediated reduction in CKD-induced kidney damage.

Methods: Eight mice underwent 5/6 nephrectomy to induce CKD and eight served as healthy controls. CKD and Healthy (H) groups were further split into those receiving RS (CKDRS, n = 4; HRS, n = 4) and those on normal diet (CKD, n = 4, H, n = 4). Kidney injury was evaluated by measuring BUN/creatinine and by histopathological evaluation. Cecal contents were analyzed using mass spectrometry-based metaproteomics and de novo sequencing using PEAKS. All the data were analyzed using R/Bioconductor packages.

Results: The 5/6 nephrectomy compromised kidney function as seen by an increase in BUN/creatinine compared to healthy groups. Histopathology of kidney sections showed reduced tubulointerstitial injury in the CKDRS versus CKD group; while no significant difference in BUN/creatinine was observed between the two CKD groups. Identified proteins point toward a higher population of butyrate-producing bacteria, reduced abundance of mucin-degrading bacteria in the RS fed groups, and to the downregulation of indole metabolism in CKD groups.

Conclusion: RS slows the progression of chronic kidney disease. Resistant starch supplementation leads to active bacterial proliferation and the reduction of harmful bacterial metabolites.

Keywords: 5/6 nephrectomy; chronic kidney disease; metaproteomics; microbiome; microbiota; resistant starch.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteria / metabolism
  • Blood Urea Nitrogen
  • Disease Models, Animal
  • Disease Progression
  • Gastrointestinal Microbiome / physiology*
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Male
  • Mice
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / physiopathology
  • Resistant Starch / metabolism*


  • Resistant Starch