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

Abstract

Abstract 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