title: In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease.
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.
authors.affiliation: Kibow Biotech Inc., 3701 Market Street, Philadelphia, PA 19104, USA.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Ranganathan
authors.forename: Beena G
authors.initials: BG
authors.lastname: Patel
authors.forename: Pari
authors.initials: P
authors.lastname: Ranganathan
authors.forename: Joseph
authors.initials: J
authors.lastname: Marczely
authors.forename: Rahul
authors.initials: R
authors.lastname: Dheer
authors.forename: Bohdan
authors.initials: B
authors.lastname: Pechenyak
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Dunn
authors.forename: Willy
authors.initials: W
authors.lastname: Verstraete
authors.forename: Karel
authors.initials: K
authors.lastname: Decroos
authors.forename: Raj
authors.initials: R
authors.lastname: Mehta
authors.forename: Eli A
authors.initials: EA
authors.lastname: Friedman
mesh_terms: D000818:Animals; D019149:Bioreactors / Q000382:microbiology; D001806:Blood Urea Nitrogen; D001835:Body Weight; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines / Q000382:microbiology*; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D009392:Nephrectomy; D010865:Pilot Projects; D019936:Probiotics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013534:Survival; D014508:Urea / Q000378:metabolism; D014511:Uremia / Q000378:metabolism / Q000382:microbiology
chemical_list: D014508:Urea