Recombinant Lactobacillus plantarum expressing and secreting heterologous oxalate decarboxylase prevents renal calcium oxalate stone deposition in experimental rats

Abstract

BackgroundCalcium oxalate (CaOx) is the major constituent of about 75% of all urinary stone and the secondary hyperoxaluria is a primary risk factor. Current treatment options for the patients with hyperoxaluria and CaOx stone diseases are limited. Oxalate degrading bacteria might have beneficial effects on urinary oxalate excretion resulting from decreased intestinal oxalate concentration and absorption. Thus, the aim of the present study is to examine the in vivo oxalate degrading ability of genetically engineered Lactobacillus plantarum (L. plantarum) that constitutively expressing and secreting heterologous oxalate decarboxylase (OxdC) for prevention of CaOx stone formation in rats. The recombinants strain of L. plantarum that constitutively secreting (WCFS1OxdC) and non-secreting (NC8OxdC) OxdC has been developed by using expression vector pSIP401. The in vivo oxalate degradation ability for this recombinants strain was carried out in a male wistar albino rats. The group I control; groups II, III, IV and V rats were fed with 5% potassium oxalate diet and 14th day onwards group II, III, IV and V were received esophageal gavage of L. plantarum WCFS1, WCFS1OxdC and NC8OxdC respectively for 2-week period. The urinary and serum biochemistry and histopathology of the kidney were carried out. The experimental data were analyzed using one-way ANOVA followed by Duncan’s multiple-range test.ResultsRecombinants L. plantarum constitutively express and secretes the functional OxdC and could degrade the oxalate up to 70–77% under in vitro. The recombinant bacterial treated rats in groups IV and V showed significant reduction of urinary oxalate, calcium, uric acid, creatinine and serum uric acid, BUN/creatinine ratio compared to group II and III rats (P < 0.05). Oxalate levels in kidney homogenate of groups IV and V were showed significant reduction than group II and III rats (P < 0.05). Microscopic observations revealed a high score (4+) of CaOx crystal in kidneys of groups II and III, whereas no crystal in group IV and a lower score (1+) in group V.ConclusionThe present results indicate that artificial colonization of recombinant strain, WCFS1OxdC and NC8OxdC, capable of reduce urinary oxalate excretion and CaOx crystal deposition by increased intestinal oxalate degradation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-014-0086-y) contains supplementary material, which is available to authorized users.

Oral administration of indigenous oxalate degrading lactic acid bacteria and quercetin prevents calcium oxalate stone formation in rats fed with oxalate rich diet

“…LAB administered rats showed normal morphology of renal tissue and decreased crystal deposition compared to rats fed with KOx. The obtained result suggests that colonization of administered LAB consumes intestinal oxalate that leads to decreased crystal deposition in kidney, this is similar with previous studies (Kwak et al, 2006;Sasikumar et al, 2014). Mild inflammation and reduced crystal deposition in QE treated rats revealed that oxalate toxicity is reduced by the antioxidant action of quercetin.…”

Lactobacillus helveticus and Lactobacillus plantarum modulate renal antioxidant status in a rat model of fructose-induced metabolic syndrome

“…The correction of these abnormalities by L. helveticus and L. plantarum supplementation could be valuable in prevention of the disease. Previously, it has been demonstrated that probiotic therapy with L. plantarum strains improves urinary oxalate, calcium, uric acid, creatinine and serum uric acid levels in rats with increased renal calcium oxalate deposition [35]. A diet rich in fructose can lead to the induction of marked oxidative stress and mitochondrial dysfunction [36].…”

Renal tubular injury induced by ischemia promotes the formation of calcium oxalate crystals in rats with hyperoxaluria

“…The subsequent formation of CaOx crystals may account for kidney stone formation. As proposed previously, hyperoxaluria is considered a major risk factor for urinary stone, and experimental induction of hyperoxaluria can lead to crystalluria and CaOx crystal deposition in the kidney [6,7]. In addition, recurrent idiopathic stone formers always show mild hyperoxaluria; meanwhile, amount and size of CaOx crystals, alongside disease severity, are highly related to urinary excretion of oxalate (Ox) [8].…”