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

Abstract

BackgroundHyperoxaluria and oxalate kidney stones frequently develop after Roux-en-Y gastric bypass (RYGB). Oxalobacter formigenes can degrade ingested oxalate. ObjectivesExamine the effect of O. formigenes wild rat strain (OXWR) colonization on urinary oxalate excretion and intestinal oxalate transport in a hyperoxaluric RYGB model. SettingBasic Science Laboratory, United States. MethodsAt 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. ResultsRYGB 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. ConclusionsIn 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.