Gut Based Uremia Therapy: Continued in Vitro and in Vivo R&D Investigations on the Application of Oral Probiotic Bacteriotherapy Towards Chronic Kidney Disease (CKD) Patients
Patel B1, Marczely J1, Ranganathan P1, Dheer R1, Ranganathan N1, Van de Wiele T2, Verstraete W2 – Handa R, Willis LR – Indiana University, Indianapolis, IN, Friedman EA
Kibow Biotech Inc, Philadelphia, PA., 2Ghent University, Gent, Belgium, Downstate Medical Center, SUNY, Brooklyn, NY 12th International Congress on Nutrition and Metabolism in Renal Disease – Free Communication FC-A8
In continuation of our earlier bowel based concept, R&D and findings, we are developing and scientifically validating an orally consumable microbial dietary supplemental probiotic product formulation which is specifically targeted to catabolize and remove several surrogate uremic toxins such as urea, creatinine, uric acid and possibly others. The microbial formulation was made by a combination of specifically screened, selected and cultured probiotics (microbes present in the commonly found fermented foods). This oral product formulation is made from a specific combination of one to four freeze dried microbial probiotic strains. The in vitro studies were performed in a similar methodology1 with the Simulator Human Intestinal Microbial Ecosystem – a computer controlled five step biochemical reactor system mimicking the gastrointestinal track of the humans.
The in vivo studies were performed with a specially bred Gottingen mini pigs of approx 3 months old and weighing between 10 to 20 lbs. Approximately 5/6th portions of both kidneys – one whole kidney plus 2/3 of the second portion of the kidney was removed. This 5/6th Nephrectomized mini pigs is a better model of human End Stage Renal Disease status (ESRD) than our previous investigations performed with 5/6th Nephrectomized rats and reported earlier2. In vitro: SHIME R&D studies provide detailed and valuable data in assessing the microbial characteristics and in formulating a suitable cocktail of probiotics for uremia therapy investigations. In vivo: Of the several probiotic oral formulations tested, a specific formulation of four microbial strains on a low frequency dosage regimen in the 5/6th Nephrectomized Minipigs (n=12) generally exhibited continued weight gain and decreased or stabilization of several biochemical parameters such as urea, creatinine, uric acid and hematocrit, reflecting that nitrogenous waste is not accumulating in the blood. This studies will elaborate and discuss in the context of gut based uremia therapy and its R&D investigations towards a potential oral theapy for pre-dialysis or CKD patients populations worldwide. These results suggest that a suitable combination of selectively chosen probiotic microbes may be suitable for oral gut based uremia therapy. Further human clinical trials are strongly suggested.