In Vitro and In Vivo Assessment of Intraintestinal Bacteriotherapy in Chronic Kidney Disease

Authors:
  • BPBeena G. Patel
    Beena G. Patel
  • PRPari Ranganathan
    Pari Ranganathan
  • JMJoseph Marczely
    Joseph Marczely
  • RDRahul Dheer
    Rahul Dheer
  • BPBohdan Pechenyak
    Bohdan Pechenyak
  • SDStephen R. Dunn
    Stephen R. Dunn
  • WVWilly Verstraete
    Willy Verstraete
  • KDKarel Decroos
    Karel Decroos
  • RMRaj Mehta
    Raj Mehta
  • EFEli A. Friedman
    Eli A. Friedman
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Abstract
Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney transplantation. No generally applicable therapies to slow progression of renal disease are available. Bacteriotherapy affords a promising approach to mitigate uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne alkalophilic urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such "enteric dialysis" formulation. Data presented herein suggest that Sp survives through exposure to gastric juice retaining the ability to hydrolyze urea. In vitro, 10 cfu (colony forming units) of Sp removed from 21 +/- 4.7 mg to 228 +/- 6.7 mg urea per hour, depending on pH, urea concentration, and nutrient availability. Beneficial effects of Sp on fermentation parameters in the intestine were demonstrated in vitro in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) inoculated with fecal microbiota. Enumeration of marker organisms suggested that presence of Sp does not disturb microbial community of the SHIME. Additionally, a pilot study in 5/6th nephrectomized rats fed 10 cfu of live Sp daily throughout the study demonstrated that the tested regimen reduced blood urea-nitrogen levels and significantly prolonged the lifespan of uremic animals.

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