Gut-Based Uremia Therapy : In vitro R&D Investigations of an Oral Probiotic Microbial Formulation with the Aid of a Simulated Human Intestinal Microbial Ecosystem (SHIME) Biochemical Reactor
Beena Patel, Ph.D.1, Olga Zelenaia, Ph.D.1, Rahul Dheer, B.S.1, Natarajan Ranganathan, Ph.D.1, Tom Van de Wiele, Ph.D.2, Willy Verstraete, Ph.D.2, Eli A. Friedman, M.D.3 1
1Kibow Biotech, Inc. Philadelphia, USA, 2Ghent State University, Ghent, Belgium, 3Downstate Medical Center, Brooklyn, USA.
International Society of Nephrology 2004 Conference on Prevention of Progression of Renal Disease – Poster #72110
In our earlier R&D investigation in rats, we further tested the hypothesis on mini pigs that ingestion of a combination of probiotic microbial strains instilled into the gastrointestinal track might efficiently convert nitrogenous wastes accumulated in renal insufficiency into non-toxic compounds. Specially bred Gottingen mini pigs of approximately three months old and weighing about ten to twenty pounds were procured and housed for two to eight weeks prior to nephrectomy surgery. Approximately 5/6th portions of both the kidneys were removed. This 5/6th nephrectomized mini pig is a better model of the human end stage renal disease status (ESRD – approximately 85% loss of kidney function).
After surgery, the animals were allowed to recuperate (for approximately two to three weeks), needed food, medication and water was provided. At several interval days, blood was withdrawn and analyzed for blood urea nitrogen (BUN), creatinine and hematocrit count. After this ESRD model confirmation, each animal was also administered and oral bacteriotherapy in increased dosage either as gel caps or admixed with food. Periodical physical examinations were given and blood was monitored for eight to twelve weeks. Of the several probiotic formulations tested, a specific formulation of four microbial strains on a low frequency dosage regimen in these 5/6th nephrectomized mini pigs (n=6) exhibited (a) continued gain in weight, approximately 33% (b) stabilization and/or somewhat decreased BUN (decrease by 13%) and creatinine (decrease by 3%) levels reflecting that nitrogenous wastes were not accumulating in the blood. This results suggests that a combination of selectively chosen probiotic microbes may be suitable for the application of gut based uremia therapy. Additional investigations need to be undertaken on a larger number of mini pigswith mor controls placed on the experiment. If there is a continued success on these probiotic oral formulations in mini pigs as seen in this study, human clinical trials is strongly suggested for assessing the concept of gut based uremia therapy.
