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.

Lactobacillus bulgaricusmutants decompose uremic toxins

“…2,3 Ranganathan et al 4 had isolated a Sporosarcina pasteurii (sp) in the gut, which decomposed many kinds of uremic toxins. Its capacity to decompose urine toxin is close to hemodialysis, except for electrolyte imbalance, however, a large number of SP bacteria are associated with dysbacteriosis and severe infections caused by bacteria carrying antibiotic resistant plasmids, and hence contraindicated for clinical application.…”

Cloning and Expression of a Urate Oxidase and Creatinine Hydrolase Fusion Gene inEscherichia coli

“…Ranganathan et al 3 have isolated a species of bacteria from the intestine that can break down a variety of uremic toxins. An in vivo study found that this toxin clearance ability was similar to hemodialysis.…”

Quality of Life in Chronic Kidney Disease Patients Using a Synbiotic Dietary Supplement: a Survey

“…As the safety and health benefits are established, it is reasonable to anticipate that probiotic bacteria will be incorporated into a growing number of clinical regimens, either on their own or as an adjunct/part of a combined treatment, including kidney disease. Over the past 15 years, the potential utilization of oral sorbents and probiotics as complementary strategy for CKD has continuously been explored, both in vitro and in vivo [12], in rat and mini pig animal trials [13,14], in veterinary trials [15], and in human clinical trials with CKD stages 3 and 4 patients [16][17][18][19]. The first patented and proprietary probiotic dietary supplement formulation to maintain kidney health was developed in 2009 -KibowBiotics® (now Renadyl™, Kibow Biotech, Inc., Newtown Square, PA, USA), containing S.thermophilus KB 19, L.acidophilus KB 27 and B.longum KB 31 strains, with a total of 45 billion colony forming units (CFU) per capsule.…”

“…Throughout the entire R&D process, Renadyl™ has shown the ability to utilize various nitrogenous uremic toxins as nutrients for growth of the beneficial gut microbial population, thus keeping the toxins from accumulating to highly toxic levels in patients with CKD. Unlike many untested probiotic supplements available on the market, Renadyl™ has the advantage of having proven scientific validity [12][13][14][15][16][17][18][19]. The results of the randomized human clinical study in ESRD patients (CKD stage 5) on hemodialysis clearly indicated the safety of usage of Renadyl with reduction in the gut derived uremic toxins like indoxyl glucuronide [20].…”