Effectiveness of Probiotics to Treat End Stage Renal Disease

Summary

Intestinal microbiota has recently emerged as an important player in the progression and complications of chronic kidney disease(CKD). And drug therapy which selects the gut as a target has raised lots of concern. It has been reported that the composition of intestinal flora has changed in uremic patients. Specifically, imbalanced ecosystem has higher number of pathogens such as Clostridia, Enterobacteria,and lower number of beneficial microbes such as Lactobacilli and Bifidobacteria. This modification of intestinal flora can strongly increase transformation of amino acids into Uremic Retention solutes, e.g., indoxyl-sulfate (IS), p-cresyl sulfate (PCS), which are so called gut-derived uremic toxins. The dysbiosis also contributes to an increase in intestinal permeability by disrupting the colonic epithelial tight junction,which may subsequently lead to translocation of endotoxin and bacteria into the host's internal environment,resulting in systemic micro-inflammation.Also all of these can promote the progression of renal failure and the incidence of cardiovascular complications,renal osteodystrophy and anemia.Probiotics is defined by the World Health Organization as 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host'. Probiotics are being increasingly used for various pathologic conditions.It is said that probiotics have a therapeutic role in maintaining a metabolically balanced gastrointestinal tract (GIT).And in our previous study,the investigators found that in uremic rats,lactobacillus acidophilus can relieve bacterial translocation and decrease the level of inflammatory markers.So our study is mainly designed to investigate whether probiotics can modulate the balance of intestinal ecosystem, prevent the bacterial translocation from gut and alleviate the systemic inflammation in hemodialysis(HD) patients.

Timeline

Start

2016-12

Primary completion

2018-01-30

Completion

2018-03-30

Publications

• Background Hida M, Aiba Y, Sawamura S, Suzuki N, Satoh T, Koga Y. Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis. Nephron. 1996;74(2):349-55. doi: 10.1159/000189334.
• Background Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, Ni Z, Nguyen TH, Andersen GL. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013 Feb;83(2):308-15. doi: 10.1038/ki.2012.345. Epub 2012 Sep 19.
• Background Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int. 2015 Nov;88(5):958-66. doi: 10.1038/ki.2015.255. Epub 2015 Sep 16.
• Background Vaziri ND, Yuan J, Rahimi A, Ni Z, Said H, Subramanian VS. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant. 2012 Jul;27(7):2686-93. doi: 10.1093/ndt/gfr624. Epub 2011 Nov 29.
• Background Shi K, Wang F, Jiang H, Liu H, Wei M, Wang Z, Xie L. Gut bacterial translocation may aggravate microinflammation in hemodialysis patients. Dig Dis Sci. 2014 Sep;59(9):2109-17. doi: 10.1007/s10620-014-3202-7. Epub 2014 May 15.
• Background Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology (Carlton). 2012 Nov;17(8):733-8. doi: 10.1111/j.1440-1797.2012.01647.x.
• Background Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T, Jorres A, Lemke HD, Massy ZA, Passlick-Deetjen J, Rodriguez M, Stegmayr B, Stenvinkel P, Tetta C, Wanner C, Zidek W; European Uremic Toxin Work Group (EUTox). Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003 May;63(5):1934-43. doi: 10.1046/j.1523-1755.2003.00924.x.
• Background Dou L, Cerini C, Brunet P, Guilianelli C, Moal V, Grau G, De Smet R, Vanholder R, Sampol J, Berland Y. P-cresol, a uremic toxin, decreases endothelial cell response to inflammatory cytokines. Kidney Int. 2002 Dec;62(6):1999-2009. doi: 10.1046/j.1523-1755.2002.t01-1-00651.x.
• Background Niwa T, Ise M, Miyazaki T. Progression of glomerular sclerosis in experimental uremic rats by administration of indole, a precursor of indoxyl sulfate. Am J Nephrol. 1994;14(3):207-12. doi: 10.1159/000168716.
• Background Food and Agriculture Organsization. Guidelines for the Evaluation of Probiotics in Food. Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food. Food and Agriculture Organization: London, 2002.
• Background Ebel B, Lemetais G, Beney L, Cachon R, Sokol H, Langella P, Gervais P. Impact of probiotics on risk factors for cardiovascular diseases. A review. Crit Rev Food Sci Nutr. 2014;54(2):175-89. doi: 10.1080/10408398.2011.579361.
• Background Wei M, Wang Z, Liu H, Jiang H, Wang M, Liang S, Shi K, Feng J. Probiotic Bifidobacterium animalis subsp. lactis Bi-07 alleviates bacterial translocation and ameliorates microinflammation in experimental uraemia. Nephrology (Carlton). 2014 Aug;19(8):500-6. doi: 10.1111/nep.12272.

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