Abstract
Hyperoxaluria significantly increases the risk of calcium oxalate kidney stone formation. Since several bacteria have been shown to metabolize oxalate in vitro, including probiotic bifidobacteria, we focused on the efficiency and possible mechanisms by which bifidobacteria can influence oxalate handling in vivo, especially in the intestines, and compared these results with the reported effects of Oxalobacter formigenes. Bifidobacterium animalis subsp. lactis DSM 10140 and B. adolescentis ATCC 15703 were administered to wild-type (WT) mice and to mice deficient in the hepatic enzyme alanine-glyoxylate aminotransferase (Agxt −/−, a mouse model of Primary Hyperoxaluria) that were fed an oxalate-supplemented diet. The administration of B. animalis subsp. lactis led to a significant decrease in urinary oxalate excretion in WT and Agxt −/− mice when compared to treatment with B. adolescentis. Detection of B. animalis subsp. lactis in feces revealed that 3 weeks after oral gavage with the bacteria 64 % of WT mice, but only 37 % of Agxt −/− mice were colonized. Examining intestinal oxalate fluxes showed there were no significant changes to net oxalate secretion in colonized animals and were therefore not associated with the changes in urinary oxalate excretion. These results indicate that colonization with B. animalis subsp. lactis decreased urinary oxalate excretion by degrading dietary oxalate thus limiting its absorption across the intestine but it did not promote enteric oxalate excretion as reported for O. formigenes. Preventive or therapeutic administration of B. animalis subsp. lactis appears to have some potential to beneficially influence dietary hyperoxaluria in mice.
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References
Weinman EJ, Frankfurt SJ, Ince A, Sansom S (1978) Renal tubular transport of organic acids. Studies with oxalate and para-aminohippurate in the rat. J Clin Investig 61(3):801–806
Voss S, Hesse A, Zimmermann DJ, Sauerbruch T, von Unruh GE (2006) Intestinal oxalate absorption is higher in idiopathic calcium oxalate stone formers than in healthy controls: measurements with the [(13) C2] oxalate absorption test. J Urol 175(5):1711–1715
Scales CD Jr, Smith AC, Hanley JM, Saigal CS, Urologic Diseases in America P (2012) Prevalence of kidney stones in the United States. Eur Urol 62(1):160–165
Danpure CJ (2005) Molecular etiology of primary hyperoxaluria type 1: new directions for treatment. Am J Nephrol 25(3):303–310
Magwira CA, Kullin B, Lewandowski S, Rodgers A, Reid SJ, Abratt VR (2012) Diversity of faecal oxalate-degrading bacteria in black and white South African study groups: insights into understanding the rarity of urolithiasis in the black group. J Appl Microbiol 113(2):418–428
Mikami K, Akakura K, Takei K, Ueda T, Mizoguchi K, Noda M, Miyake M, Ito H (2003) Association of absence of intestinal oxalate degrading bacteria with urinary calcium oxalate stone formation. Int J Urol 10(6):293–296
Sidhu H, Schmidt ME, Cornelius JG, Thamilselvan S, Khan SR, Hesse A, Peck AB (1999) Direct correlation between hyperoxaluria/oxalate stone disease and the absence of the gastrointestinal tract-dwelling bacterium Oxalobacter formigenes: possible prevention by gut recolonization or enzyme replacement therapy. J Am Soc Nephrol 10(Suppl 14):S334–S340
Allison MJ, Dawson KA, Mayberry WR, Foss JG (1985) Oxalobacter formigenes gen. nov., sp. nov.: oxalate-degrading anaerobes that inhabit the gastrointestinal tract. Arch Microbiol 141(1):1–7
Duncan SH, Richardson AJ, Kaul P, Holmes RP, Allison MJ, Stewart CS (2002) Oxalobacter formigenes and its potential role in human health. Appl Environ Microbiol 68(8):3841–3847
Hatch M, Cornelius J, Allison M, Sidhu H, Peck A, Freel RW (2006) Oxalobacter sp. reduces urinary oxalate excretion by promoting enteric oxalate secretion. Kidney Int 69(4):691–698
Hatch M, Freel RW (2013) A human strain of Oxalobacter (HC-1) promotes enteric oxalate secretion in the small intestine of mice and reduces urinary oxalate excretion. Urolithiasis 41(5):379–384
Hatch M, Gjymishka A, Salido EC, Allison MJ, Freel RW (2011) Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter. Am J Physiol Gastrointest Liv Physiol 300(3):G461–G469
Hoppe B, Beck B, Gatter N, von Unruh G, Tischer A, Hesse A, Laube N, Kaul P, Sidhu H (2006) Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1. Kidney Int 70(7):1305–1311
Hoppe B, Groothoff JW, Hulton SA, Cochat P, Niaudet P, Kemper MJ, Deschenes G, Unwin R, Milliner D (2011) Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria. Nephrol Dial Transplant 26(11):3609–3615
Lewandowski S, Rodgers AL, Laube N, von Unruh G, Zimmermann D, Hesse A (2005) Oxalate and its handling in a low stone risk vs a stone-prone population group. World J Urol 23(5):330–333
Rodgers A (2006) The riddle of kidney stone disease: lessons from Africa. Urol Res 34(2):92–95
Federici F, Vitali B, Gotti R, Pasca MR, Gobbi S, Peck AB, Brigidi P (2004) Characterization and heterologous expression of the oxalyl coenzyme A decarboxylase gene from Bifidobacterium lactis. Appl Environ Microbiol 70(9):5066–5073
Turroni S, Bendazzoli C, Dipalo SC, Candela M, Vitali B, Gotti R, Brigidi P (2010) Oxalate-degrading activity in Bifidobacterium animalis subsp. lactis: impact of acidic conditions on the transcriptional levels of the oxalyl coenzyme A (CoA) decarboxylase and formyl-CoA transferase genes. Appl Environ Microbiol 76(16):5609–5620
Turroni S, Vitali B, Bendazzoli C, Candela M, Gotti R, Federici F, Pirovano F, Brigidi P (2007) Oxalate consumption by lactobacilli: evaluation of oxalyl-CoA decarboxylase and formyl-CoA transferase activity in Lactobacillus acidophilus. J Appl Microbiol 103(5):1600–1609
Kwak C, Jeong BC, Ku JH, Kim HH, Lee JJ, Huh CS, Baek YJ, Lee SE (2006) Prevention of nephrolithiasis by Lactobacillus in stone-forming rats: a preliminary study. Urol Res 34(4):265–270
Murphy C, Murphy S, O’Brien F, O’Donoghue M, Boileau T, Sunvold G, Reinhart G, Kiely B, Shanahan F, O’Mahony L (2009) Metabolic activity of probiotics-oxalate degradation. Vet Microbiol 136(1–2):100–107
Heuvelin E, Lebreton C, Bichara M, Cerf-Bensussan N, Heyman M (2010) A Bifidobacterium probiotic strain and its soluble factors alleviate chloride secretion by human intestinal epithelial cells. J Nutr 140(1):7–11
Raheja G, Singh V, Ma K, Boumendjel R, Borthakur A, Gill RK, Saksena S, Alrefai WA, Ramaswamy K, Dudeja PK (2010) Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism. Am J Physiol Gastrointest Liver Physiol 298(3):G395–G401
Xu H, Zisman AL, Coe FL, Worcester EM (2013) Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother 14(4):435–447
Campieri C, Campieri M, Bertuzzi V, Swennen E, Matteuzzi D, Stefoni S, Pirovano F, Centi C, Ulisse S, Famularo G, De Simone C (2001) Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration. Kidney Int 60(3):1097–1105
Siener R, Bade DJ, Hesse A, Hoppe B (2013) Dietary hyperoxaluria is not reduced by treatment with lactic acid bacteria. J Transl Med 11:306
Al-Wahsh I, Wu Y, Liebman M (2012) Acute probiotic ingestion reduces gastrointestinal oxalate absorption in healthy subjects. Urol Res 40(3):191–196
Ferraz RR, Marques NC, Froeder L, Menon VB, Siliano PR, Baxmann AC, Heilberg IP (2009) Effects of Lactobacillus casei and Bifidobacterium breve on urinary oxalate excretion in nephrolithiasis patients. Urol Res 37(2):95–100
Goldfarb DS, Modersitzki F, Asplin JR (2007) A randomized, controlled trial of lactic acid bacteria for idiopathic hyperoxaluria. Clin J Am Soc Nephrol 2(4):745–749
Lieske JC, Goldfarb DS, De Simone C, Regnier C (2005) Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int 68(3):1244–1249
Lieske JC, Tremaine WJ, De Simone C, O’Connor HM, Li X, Bergstralh EJ, Goldfarb DS (2010) Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation. Kidney Int 78(11):1178–1185
Okombo J, Liebman M (2010) Probiotic-induced reduction of gastrointestinal oxalate absorption in healthy subjects. Urol Res 38(3):169–178
Salido EC, Li XM, Lu Y, Wang X, Santana A, Roy-Chowdhury N, Torres A, Shapiro LJ, Roy-Chowdhury J (2006) Alanine-glyoxylate aminotransferase-deficient mice, a model for primary hyperoxaluria that responds to adenoviral gene transfer. Proc Natl Acad Sci USA 103(48):18249–18254
Heinegard D, Tiderstrom G (1973) Determination of serum creatinine by a direct colorimetric method. Clin Chim Acta 43(3):305–310
Junick J, Blaut M (2012) Quantification of human fecal bifidobacterium species by use of quantitative real-time PCR analysis targeting the groEL gene. Appl Environ Microbiol 78(8):2613–2622
Freel RW, Hatch M, Green M, Soleimani M (2006) Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice. Am J Physiol Gastrointest Liver Physiol 290(4):G719–G728
Miller A, Dearing D (2013) The metabolic and ecological interactions of oxalate-degrading bacteria in the mammalian gut. Pathogens 2(4):636–652
Conway PL (1996) Selection criteria for probiotic microorganisms. Asia Pac J Clin Nutr 5(1):10–14
Lange JN, Wood KD, Wong H, Otto R, Mufarrij PW, Knight J, Akpinar H, Holmes RP, Assimos DG (2012) Sensitivity of human strains of Oxalobacter formigenes to commonly prescribed antibiotics. Urology 79(6):1286–1289
Mittal RD, Kumar R, Bid HK, Mittal B (2005) Effect of antibiotics on Oxalobacter formigenes colonization of human gastrointestinal tract. J Endourol 19(1):102–106
Acknowledgments
The authors thank Tisha Van Pelt and Heran Getachew for excellent technical assistance and Dr. Robert W. Freel for comments on the manuscript. This study was supported by National Institute of Health grant DK 088892 and by The Oxalosis and Hyperoxaluria Foundation.
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The authors declare that they have no conflict of interest.
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Klimesova, K., Whittamore, J.M. & Hatch, M. Bifidobacterium animalis subsp. lactis decreases urinary oxalate excretion in a mouse model of primary hyperoxaluria. Urolithiasis 43, 107–117 (2015). https://doi.org/10.1007/s00240-014-0728-2
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DOI: https://doi.org/10.1007/s00240-014-0728-2