Skip to main content
Log in

Presence of Oxalobacter formigenes in the intestinal tract is associated with the absence of calcium oxalate urolith formation in dogs

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

The incidence of calcium oxalate (CaOx) urolithiasis in dogs has increased steadily over the last two decades. A potential mechanism to minimize CaOx urolithiasis is to reduce enteric absorption of dietary oxalate by oxalate-metabolizing enteric bacteria. Enteric colonization of Oxalobacter formigenes, an anaerobe which exclusively relies on oxalate metabolism for energy, is correlated with absence of hyperoxaluria or CaOx urolithiasis or both in humans and laboratory animals. We thus hypothesized that decreased enteric colonization of O. formigenes is a risk factor for CaOx urolithiasis in dogs. Fecal samples from dogs with CaOx uroliths, clinically healthy, age-, breed- and gender-matched dogs, and healthy non-stone forming breed dogs were screened for the presence of O. formigenes by quantitative PCR to detect the oxalyl CoA decarboxylase (oxc) gene, and by oxalate degrading biochemical activity in fecal cultures. Prevalence of O. formigenes in dogs with CaOx uroliths was 25%, compared to 50% in clinically healthy, age-, breed- and gender-matched dogs, and 75% in healthy non-stone forming breeds. The presence of oxc genes of O. formigenes was significantly higher in healthy non-stone forming breed dogs than in the dogs with CaOx stones. Further, dogs with calcium oxalate stones and the stone-forming breed-matched controls showed comparable levels of biochemical oxalate degrading activity. We conclude that the absence of enteric colonization of O. formigenes is a risk factor for CaOx urolithiasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

PCR:

Polymerase chain reaction

References

  1. Abratt VR, Reid SJ (2010) Oxalate-degrading bacteria of the human gut as probiotics in the management of kidney stone disease. Adv Appl Microbiol 72:63–87

    Article  PubMed  CAS  Google Scholar 

  2. Allison MJ, Cook HM, Milne DB, Gallagher S, Clayman RV (1986) Oxalate degradation by gastrointestinal bacteria from humans. J Nutr 116:455–460

    PubMed  CAS  Google Scholar 

  3. 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 141:1–7

    Article  PubMed  CAS  Google Scholar 

  4. Allison MJ, Cook HM (1981) Oxalate degradation by microbes of the large bowel of herbivores: the effect of dietary oxalate. Science 212:675–676

    Article  PubMed  CAS  Google Scholar 

  5. Daniel SL, Hartman PA, Allison MJ (1987) Microbial degradation of oxalate in the gastrointestinal tracts of rats. Appl Environ Microbiol 53:1793–1797

    PubMed  CAS  Google Scholar 

  6. Dawson KA, Allison MJ, Hartman PA (1980) Isolation and some characteristics of anaerobic oxalate-degrading bacteria from the rumen. Appl Environ Microbiol 40:833–839

    PubMed  CAS  Google Scholar 

  7. Dobbins JW, Binder HJ (1976) Effect of bile salts and fatty acids on the colonic absorption of oxalate. Gastroenterology 70:1096–1100

    PubMed  CAS  Google Scholar 

  8. 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 68:3841–3847

    Article  PubMed  CAS  Google Scholar 

  9. 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 Liver Physiol 300(3):G461–G469

    Article  PubMed  CAS  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 69:691–698

    Article  PubMed  CAS  Google Scholar 

  11. Holmes RP, Goodman HO, Assimos DG (2001) Contribution of dietary oxalate to urinary oxalate excretion. Kidney Int 59:270–276

    Article  PubMed  CAS  Google Scholar 

  12. 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 26:3609–3615

    Article  PubMed  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 70:1305–1311

    Article  PubMed  CAS  Google Scholar 

  14. Kaufman DW, Kelly JP, Curhan GC, Anderson TE, Dretler SP, Preminger GM, Cave DR (2008) Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones. J Am Soc Nephrol 19:1197–1203

    Article  PubMed  CAS  Google Scholar 

  15. Kelly JP, Curhan GC, Cave DR, Anderson TE, Kaufman DW (2011) Factors related to colonization with Oxalobacter formigenes in US adults. J Endourol 25:673–679

    Article  PubMed  Google Scholar 

  16. Knight J, Jiang J, Wood KD, Holmes RP, Assimos DG (2011) Oxalate and sucralose absorption in idiopathic calcium oxalate stone formers. Urology 78:475.e9–475.e13

    Article  Google Scholar 

  17. Kwak C, Kim HK, Kim EC, Choi MS, Kim HH (2003) Urinary oxalate levels and the enteric bacterium Oxalobacter formigenes in patients with calcium oxalate urolithiasis. Eur Urol 44:475–481

    Article  PubMed  CAS  Google Scholar 

  18. Lekcharoensuk C, Osborne CA, Lulich JP, Pusoonthornthum R, Kirk CA, Ulrich LK, Koehler LA, Carpenter KA, Swanson LL (2002) Associations between dry dietary factors and canine calcium oxalate uroliths. Am J Vet Res 63(3):330–337

    Article  PubMed  CAS  Google Scholar 

  19. Lulich JP (2009) Calcium oxalate: biological behavior and risk factor management. ACVIM Forum Proceedings 27:606–607

    Google Scholar 

  20. Lulich JP, Osborne CA, Thumchai R, Lekcharoensuk C, Ulrich LK, Koehler LA, Bird KA, Swanson LL, Nakagawa Y (1999) Epidemiology of canine calcium oxalate uroliths. Identifying risk factors. Vet Clin North Am Small Anim Pract 29:113–22, xi

    Google Scholar 

  21. 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 10:293–296

    Article  PubMed  Google Scholar 

  22. Mittal RD, Kumar R, Mittal B, Prasad R, Bhandari M (2003) Stone composition, metabolic profile and the presence of the gut-inhabiting bacterium Oxalobacter formigenes as risk factors for renal stone formation. Med Princ Pract 12(4):208–213

    Article  PubMed  CAS  Google Scholar 

  23. Osborne CA, Lulich JP, Kruger JM, Ulrich LK, Koehler LA (2009) Analysis of 451,891 canine uroliths, feline uroliths, and feline urethral plugs from 1981 to 2007: perspectives from the Minnesota Urolith Center. Vet Clin North Am Small Anim Pract 39(1):183–197

    Article  PubMed  Google Scholar 

  24. Prokopovich S, Knight J, Assimos DG, Holmes RP (2007) Variability of Oxalobacter formigenes and oxalate in stool samples. J Urol 178:2186–2190

    Article  PubMed  CAS  Google Scholar 

  25. Sidhu H, Allison MJ, Chow JM, Clark A, Peck AB (2001) Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes. J Urol 166:1487–1491

    Article  PubMed  CAS  Google Scholar 

  26. Sidhu H, Holmes RP, Allison MJ, Peck AB (1999) Direct quantification of the enteric bacterium Oxalobacter formigenes in human fecal samples by quantitative competitive-template PCR. J Clin Microbiol 37:1503–1509

    PubMed  CAS  Google Scholar 

  27. 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

    PubMed  CAS  Google Scholar 

  28. Sidhu H, Hoppe B, Hesse A, Tenbrock K, Bromme S, Rietschel E, Peck AB (1998) Absence of Oxalobacter formigenes in cystic fibrosis patients: a risk factor for hyperoxaluria. Lancet 352:1026–1029

    Article  PubMed  CAS  Google Scholar 

  29. Sidhu H, Enatska L, Ogden S, Williams WN, Allison MJ, Peck AB (1997) Evaluating children in the Ukraine for colonization with the intestinal bacterium Oxalobacter formigenes, using a polymerase chain reaction-based detection system. Mol Diagn 2:89–97

    Article  PubMed  CAS  Google Scholar 

  30. Troxel SA, Sidhu H, Kaul P, Low RK (2003) Intestinal Oxalobacter formigenes colonization in calcium oxalate stone formers and its relation to urinary oxalate. J Endourol 17:173–176

    Article  PubMed  Google Scholar 

  31. Wandzilak TR, Williams HE (1990) The hyperoxaluric syndromes. Endocrinol Metab Clin North Am 19(4):851–867

    PubMed  CAS  Google Scholar 

  32. Weese JS, Palmer A (2009) Presence of Oxalobacter formigenes in the stool of healthy dogs. Vet Microbiol 137:412–413

    Article  PubMed  Google Scholar 

  33. Weese JS, Rousseau J, Weese HE (2009) Variation in shedding of Oxalobacter formigenes in feces of healthy dogs. Vet Microbiol 139:421–422

    Article  PubMed  CAS  Google Scholar 

  34. Weese JS, Weese HE, Rousseau J (2009) Identification of Oxalobacter formigenes in the faeces of healthy cats. Lett Appl Microbiol 49(6):800–802

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. M. Allison, Iowa State University, for technical advice on anaerobic culture and for kindly providing the O. formigenes-positive culture. Dr. Carl A. Osborne, Department of Veterinary Clinical Sciences, University of Minnesota, for his vision and encouragement in initiating studies of canine urolithiasis and establishing the Urolith Center through which the animals in this study were recruited. Dr. H. Albasan and staff of Minnesota Urolith Center assisted in sample collection. Dr. R. Knurr, Department of Geology and Geophysics, University of Minnesota, performed the ion chromatographic analyses. This study was funded by the Morris Animal Foundation grants D08CA-154 and DO8CA-408.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael P. Murtaugh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gnanandarajah, J.S., Abrahante, J.E., Lulich, J.P. et al. Presence of Oxalobacter formigenes in the intestinal tract is associated with the absence of calcium oxalate urolith formation in dogs. Urol Res 40, 467–473 (2012). https://doi.org/10.1007/s00240-011-0451-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00240-011-0451-1

Keywords

Navigation