Investigation of Resistant Starch effect on gut microbiome in 5/6 nephrectomy mouse model of Chronic Kidney Disease

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 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 8 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 most-mortem histopathological evaluation. Cecal contents were analyzed mass spectrometry-based metaproteomics. PEAKS Studio was used to identify peptides via de novo sequencing. A set of R/Bioconductor packages and in house written scripts was further used to infer bacteria present, to evaluate changes in proteins and bacterial abundances, and to perform statistical analysis and hierarchical clustering. Results. The 5/6 nephrectomy compromised kidney function as seen by an increase in creatinine and BUN. Representative photomicrographs of trichrome-stained kidney sections showed reduced tubulointerstitial injury in CKD mice fed HAM-RS2 diet comparing to CKD mice fed normal diet. Identified organisms and proteins point toward a higher population of butyrate-producing bacteria, and reduced abundance of mucin-degrading bacteria. Conclusion. Resistant starch slows the progression of chronic kidney disease. Gut barrier function through maintenance of the mucin barrier plays a role in RS-associated improvements in CKD phenotype. Resistant starch supplementation leads to the active bacterial proliferation and the reduction of harmful bacterial metabolites.  

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cecum

DISEASE(S): Chronic Kidney Disease

SUBMITTER: Boris Zybailov  

LAB HEAD: Boris Zybailov

PROVIDER: PXD019623 | Pride | 2020-10-19

REPOSITORIES: Pride