Streptococcus Thermophilus KB19 is a Potential Component of a Probiotic Regimen Applicable in Enteric Dialysis for Uremia
Olga A Zelenaia, Ph.D., Beena G Patel, Ph.D., Rahul S Dheer, B.S., Natarajan Ranganathan, Ph.D.
Kibow Biotech Inc., Philadelphia, PA, United States of America.
Journal of the American Society of Nephrology 14: Nov 2003 pp. 765A SU-PO1045
Kidney dysfunction, often a consequence of other multisystem disorders such as diabetes or atherosclerosis, has a broad prevalence afflicting as many as twenty million Americans. Consequent to progression to end stage renal disease (ESRD), patients in “affluent” nations are treated with a kidney transplant or dialysis, most commonly hemodialysis performed thrice weekly. Appreciating the reality that the expense ($65,000 annually per patient) of hemodialysis excludes the majority of those afflicted with ESRD, the potential of “enteric dialysis” is under evaluation.
Nitrogenous wastes that accumulate in uremia flow into the gut by passive diffusion. We are testing a formulation of commensal and food grade bateria that when ingested may become gut flora that catabolize these toxins. If effective, instillation of probiotic microbes may permit reduction in frequency and even elimination of the need for dialysis.
Three isolates of gram-positive, lactic acid producing non-pathogenic cocci Streptococcus thermophilus from different sources, strains KB4, KB19, and KB25, were characterized in vitro by assessing their ability to catabolize urea while proliferating in the simulated intestinal fluid. All three strains studied (1) proliferated in the fed state simulated artificial intestinal fluid (AIF) in the pH range from 5.5 to 7.5 characteristic of colon environment; (2) used urea as a sole nitrogen source and (3) catabolized urea in the presence of other nitrogen sources. Urea hydrolysis was growth and pH dependent. Under all the conditions tested rate of urea hydrolysis was strain-dependent permitting selection of the best candidate for uremic applications. The selected isolate S.thermophilus KB19 reduced urea concentration from 300mg/dL to 20mg/dL within 24 hours at pH 6.3 when inoculated in AIF at initial density of 10^9 cfu/ml. KB19 survived 3 hours in acidic pH 3.0 with only two logs loss in cfu and was able to pass through bile. In addition, this strain evinced no resistance to 8 commonly used antibiotics. These data indicate that a specifically selected bacterial isolate can be used as a urea-targeted component in an enteric dialysis formulation