Advertisement

Oxalobacter formigenes colonization normalizes oxalate excretion in a gastric bypass model of hyperoxaluria

      Abstract

      Background

      Hyperoxaluria and oxalate kidney stones frequently develop after Roux-en-Y gastric bypass (RYGB). Oxalobacter formigenes can degrade ingested oxalate.

      Objectives

      Examine the effect of O. formigenes wild rat strain (OXWR) colonization on urinary oxalate excretion and intestinal oxalate transport in a hyperoxaluric RYGB model.

      Setting

      Basic Science Laboratory, United States.

      Methods

      At 21 weeks of age, 28 obese male Sprague-Dawley rats survived Sham (n = 10) or RYGB (n = 18) surgery and were maintained on a 1.5% potassium oxalate, 40% fat diet. At 12 weeks postoperatively, half the animals in each group were gavaged with OXWR. At 16 weeks, percent dietary fat content was lowered to 10%. Urine and stool were collected weekly to determine oxalate and colonization status, respectively. At week 20, [14 C]-oxalate fluxes and electrical parameters were measured in vitro across isolated distal colon and jejunal (Roux limb) tissue mounted in Ussing Chambers.

      Results

      RYGB animals lost 22% total weight while Shams gained 5%. On a moderate oxalate diet, urinary oxalate excretion was 4-fold higher in RYGB than Sham controls. OXWR colonization, obtained in all gavaged animals, reduced urinary oxalate excretion 74% in RYGB and 39% in Sham and was further augmented by lowering the percentage of dietary fat. Finally, OXWR colonization significantly enhanced basal net colonic oxalate secretion in both groups.

      Conclusions

      In our model, OXWR lowered urinary oxalate by luminal oxalate degradation in concert with promotion of enteric oxalate elimination. Trials of O. formigenes colonization and low-fat diet are warranted in calcium oxalate stone formers with gastric bypass and resistant hyperoxaluria.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Surgery for Obesity and Related Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Park A.M.
        • Storm D.W.
        • Fulmer B.R.
        • Still C.D.
        • Wood G.C.
        • Hartle 2nd, J.E.
        A prospective study of risk factors for nephrolithiasis after Roux-en-Y gastric bypass surgery.
        J Urol. 2009; 182: 2334-2339
        • Duffey B.G.
        • Alanee S.
        • Pedro R.N.
        • et al.
        Hyperoxaluria is a long-term consequence of Roux-en-Y Gastric bypass: a 2-year prospective longitudinal study.
        J Am Coll Surg. 2010; 211: 8-15
        • Valezi A.C.
        • Fuganti P.E.
        • Junior J.M.
        • Delfino V.D.
        Urinary evaluation after RYGBP: a lithogenic profile with early postoperative increase in the incidence of urolithiasis.
        Obes Surg. 2013; 23: 1575-1580
        • Canales B.K.
        • Hatch M.
        Kidney stone incidence and metabolic urinary changes after modern bariatric surgery: review of clinical studies, experimental models, and prevention strategies.
        Surg Obes Relat Dis. 2014; 10: 734-742
        • Allison M.J.
        • Dawson K.A.
        • Mayberry W.R.
        • Foss J.G.
        Oxalobacter formigenes gen. nov., sp. nov.: oxalate-degrading anaerobes that inhabit the gastrointestinal tract.
        Arch Microbiol. 1985; 141: 1-7
        • Jiang J.
        • Knight J.
        • Easter L.H.
        • Neiberg R.
        • Holmes R.P.
        • Assimos D.G.
        Impact of dietary calcium and oxalate, and Oxalobacter formigenes colonization on urinary oxalate excretion.
        J Urol. 2011; 186: 135-139
        • Kaufman D.W.
        • Kelly J.P.
        • Curhan G.C.
        • et al.
        Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones.
        J Am Soc Nephrol. 2008; 19: 1197-1203
        • Siener R.
        • Bangen U.
        • Sidhu H.
        • Hönow R.
        • von Unruh G.
        • Hesse A.
        The role of Oxalobacter formigenes colonization in calcium oxalate stone disease.
        Kidney Int. 2013; 83: 1144-1149
        • Canales B.K.
        • Ellen J.
        • Khan S.R.
        • Hatch M.
        Steatorrhea and hyperoxaluria occur after gastric bypass surgery in obese rats regardless of dietary fat or oxalate.
        J Urol. 2013; 190: 1102-1109
        • Green M.L.
        • Hatch M.
        • Freel R.W.
        Ethylene glycol induces hyperoxaluria without metabolic acidosis in rats.
        Am J Physiol Renal Physiol. 2005; 289: F536-F543
        • Freel R.W.
        Dihydroxy bile salt-induced secretion of rubidium ion across the rabbit distal colon.
        Am J Physiol. 1987; 252: G554-G561
        • Hatch M.
        • Gjymishka A.
        • Salido E.C.
        • Allison M.J.
        • Freel R.W.
        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. 2011; 300: G461-G469
        • Freel R.W.
        • Hatch M.
        • Earnest D.L.
        • Goldner A.M.
        Oxalate transport across the isolated rat colon. A re-examination.
        Biochim Biophys Acta. 1980; 600: 838-843
        • Lieske J.C.
        • Goldfarb D.S.
        • De Simone C.
        • Regnier C.
        Use of a probiotic to decrease enteric hyperoxaluria.
        Kidney Int. 2005; 68: 1244-1249
        • Hoppe B.
        • Beck B.
        • Gatter N.
        • et al.
        Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1.
        Kidney Int. 2006; 70: 1305-1311
        • Hoppe B.
        • Groothoff J.W.
        • Hulton S.A.
        • et al.
        Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria.
        Nephrol Dial Transplant. 2011; 26: 3609-3615
        • Hatch M.
        • Canales B.K.
        The mechanistic basis of hyperoxaluria following gastric bypass in obese rats.
        Urolithiasis. 2016; 44: 221-230
        • Hatch M.
        • Cornelius J.
        • Allison M.
        • Sidhu H.
        • Peck A.
        • Freel R.W.
        Oxalobacter sp. reduces urinary oxalate excretion by promoting enteric oxalate secretion.
        Kidney Int. 2006; 69: 691-698
        • Hatch M.
        • Freel R.W.
        A human strain of Oxalobacter (HC-1) promotes enteric oxalate secretion in the small intestine of mice and reduces urinary oxalate excretion.
        Urolithiasis. 2013; 41: 379-384
        • Allison M.J.
        • Cook H.M.
        • Milne D.B.
        • Gallagher S.
        • Clayman R.V.
        Oxalate degradation by gastrointestinal bacteria from humans.
        J Nutrition. 1986; 116: 455-460
        • Duffey B.G.
        • Miyaoka R.
        • Holmes R.
        • et al.
        Oxalobacter colonization in the morbidly obese and correlation with urinary stone risk.
        Urology. 2011; 78: 531-534
        • Froeder L.
        • Arasaki C.H.
        • Malheiros C.A.
        • Baxmann A.C.
        • Heilberg I.P.
        Response to dietary oxalate after bariatric surgery.
        Clin J Am Soc Nephrol. 2012; 7: 2033-2040
        • Kelly J.P.
        • Curhan G.C.
        • Cave D.R.
        • Anderson T.E.
        • Kaufman D.W.
        Factors related to colonization with Oxalobacter formigenes in U.S. adults.
        J Endourol. 2011; 25: 673-679