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Kidney Week

Abstract: PO0659

Evaluation of the Effects of a Resistant Starch Diet and Metaproteomics Study of Microbiome-Host Interactions in a 5/6 Nephrectomy Murine Model of CKD

Session Information

  • CKD Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Karaduta, Oleg K., University of Arkansas System, Little Rock, Arkansas, United States
  • Glazko, Galina V., University of Arkansas System, Little Rock, Arkansas, United States
  • Dvanajscak, Zeljko, Arkana Laboratories, Little Rock, Arkansas, United States
  • Rahmatallah, Yasir, University of Arkansas System, Little Rock, Arkansas, United States
  • Mackintosh, Samuel G., University of Arkansas System, Little Rock, Arkansas, United States
  • Arthur, John M., University of Arkansas System, Little Rock, Arkansas, United States
  • Zybailov, Boris, University of Arkansas System, Little Rock, Arkansas, United States
Background

Chronic kidney disease (CKD), a progressive decline in kidney function, is a growing health problem: 13% of adults in the US have CKD. In 40% of cases, CKD leads to irreversible loss of kidney function, end-stage renal disease. Pre-biotic Resistant Starch (RS) changes gut flora and alleviates CKD. However, mechanisms of RS action remain unclear.

Methods

Male mice (n=8) were used to reduce renal mass and to induce CKD. 8 mice served as healthy controls. Each of the two groups was further split in two sub-groups (n=4, each), either supplemented with RS or regular diet. PEAKS was used to identify peptides via de novo sequencing in cecal content. To better understand the differences between CKD, CKDRS, HRS and H phenotypes we combined all bacteria that were differentially abundant in six comparisons to infer bacterial co-abundance (BCoA) network. Histopathological evaluation was used for kidney damage comparison.

Results

Histopathological evaluation showed that CKDRS mice had less kidney damage compared to CKD group.
Using metaproteomics we found that the most abundant bacterium in HRS phenotype is indole-producing Oscillibacter sp. 1-3, confirming the result of Blast2GO that indole metabolism is upregulated in HRS phenotype as compared to CKDRS and CKD. The most connected network’ hub Firmicutes bacterium ASF500 is significantly overrepresented in CKDRS as compared to CKD and is not significantly different between HRS and H. Firmicutes bacterium ASF500 belongs to 20 bacterial strains from human intestine that can induce Th17 cells in the mouse and rat intestine and have immunostimulatory effects.
Experiments to validate effect of butyrate on host epithelial cells in germ-free mice are underway.

Conclusion

Resistant starch slows down the progression of chronic kidney disease in 5/6 nephrectomy model. For the first time we demonstrate decrease in kidney fibrosis during RS supplementation. Metaproteomics allows to discover molecular mechanisms and bacterial species responsible for beneficial effects of RS. MST2 analysis allows for clear visualization of the most important connections within the bacterial co-abundance network.

Funding

  • Other NIH Support