In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease
In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease
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DOI：
10.1097/01.mat.0000191345.45735.00
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发表时间：
2006-01-01
期刊：
影响因子：
4.2
通讯作者：
Friedman, EA
中科院分区：
文献类型：
--
作者：
Ranganathan, N;Patel, BG;Friedman, EA
慢性肾脏疾病可能进展为终末期肾脏疾病，需要透析或肾移植。目前尚无减缓肾脏疾病进展的普遍适用疗法。细菌疗法提供了一种有前途的方法，以减轻尿毒症中毒的摄入活的微生物能够分解代谢尿毒症溶质在肠道。本研究评价了非致病性土壤嗜碱尿素酶阳性细菌巴氏孢子八叠球菌（Sp）作为这种“肠透析”制剂的潜在尿素靶向组分。本文提供的数据表明，Sp通过暴露于胃液而存活，保留了水解尿素的能力。在体外，10（9）cfu（菌落形成单位）的Sp从每小时21 +/- 4.7 mg至228 +/- 6.7 mg尿素清除，具体取决于pH值、尿素浓度和营养素可用性。在接种粪便微生物群的人肠道微生物生态系统模拟器（SHIME）中，体外证明了Sp对肠道发酵参数的有益影响。计数的标记生物表明，SP的存在并不扰乱微生物群落的SHIME。此外，在5/6肾切除大鼠中进行的一项初步研究表明，在整个研究期间，每天喂食10（9）cfu活Sp，试验方案降低了血液尿素氮水平，并显著延长了尿毒症动物的寿命。
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(9) 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(9) 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.