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Bifidobacterium animalis subsp. lactis decreases urinary oxalate excretion in a mouse model of primary hyperoxaluria

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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

  1. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. 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

    Article  CAS  PubMed  Google Scholar 

  3. 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

    Article  PubMed Central  PubMed  Google Scholar 

  4. Danpure CJ (2005) Molecular etiology of primary hyperoxaluria type 1: new directions for treatment. Am J Nephrol 25(3):303–310

    Article  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed  Google Scholar 

  6. 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

    Article  PubMed  Google Scholar 

  7. 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

    CAS  PubMed  Google Scholar 

  8. 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

    Article  CAS  PubMed  Google Scholar 

  9. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. 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

    Article  CAS  PubMed  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. 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

    Article  CAS  Google Scholar 

  13. 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

    Article  CAS  PubMed  Google Scholar 

  14. 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

    Article  PubMed  Google Scholar 

  15. 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

    Article  CAS  PubMed  Google Scholar 

  16. Rodgers A (2006) The riddle of kidney stone disease: lessons from Africa. Urol Res 34(2):92–95

    Article  PubMed  Google Scholar 

  17. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. 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

    Article  CAS  PubMed  Google Scholar 

  20. 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

    Article  PubMed  Google Scholar 

  21. 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

    Article  CAS  PubMed  Google Scholar 

  22. 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

    Article  CAS  PubMed  Google Scholar 

  23. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. 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

    Article  CAS  PubMed  Google Scholar 

  26. 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

    Article  PubMed Central  PubMed  Google Scholar 

  27. Al-Wahsh I, Wu Y, Liebman M (2012) Acute probiotic ingestion reduces gastrointestinal oxalate absorption in healthy subjects. Urol Res 40(3):191–196

    Article  PubMed  Google Scholar 

  28. 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

    Article  CAS  PubMed  Google Scholar 

  29. 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

    Article  PubMed  Google Scholar 

  30. Lieske JC, Goldfarb DS, De Simone C, Regnier C (2005) Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int 68(3):1244–1249

    Article  CAS  PubMed  Google Scholar 

  31. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Okombo J, Liebman M (2010) Probiotic-induced reduction of gastrointestinal oxalate absorption in healthy subjects. Urol Res 38(3):169–178

    Article  PubMed  Google Scholar 

  33. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Heinegard D, Tiderstrom G (1973) Determination of serum creatinine by a direct colorimetric method. Clin Chim Acta 43(3):305–310

    Article  CAS  PubMed  Google Scholar 

  35. 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. 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

    Article  CAS  PubMed  Google Scholar 

  37. Miller A, Dearing D (2013) The metabolic and ecological interactions of oxalate-degrading bacteria in the mammalian gut. Pathogens 2(4):636–652

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Conway PL (1996) Selection criteria for probiotic microorganisms. Asia Pac J Clin Nutr 5(1):10–14

    CAS  PubMed  Google Scholar 

  39. 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

    Article  PubMed Central  PubMed  Google Scholar 

  40. 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

    Article  CAS  PubMed  Google Scholar 

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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.

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Klara Klimesova

    Present address: Laboratory of Cellular and Molecular Immunology, Institute of Microbiology ASCR, v.v.i., Videnska 1083, 142 20, Prague 4, Czech Republic

Authors and Affiliations

  1. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, USA

    Klara Klimesova, Jonathan M. Whittamore & Marguerite Hatch

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  1. Klara Klimesova
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  2. Jonathan M. Whittamore
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Correspondence to Klara Klimesova.

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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

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