Synbiotic supplementation and oxalate homeostasis in rats: focus on microbiota oxalate-degrading activity

Abstract

Background The present study aimed (i) to evaluate whether ceftriaxone treatment could affect not only intestinal oxalate-degrading bacteria number but their total activity to degrade oxalate and in uence oxalate homeostasis in rats, (ii) to test the effect of commercially available probiotics and a synbiotic on total fecal oxalate-degrading activity, (iii) and to estimate the ability of synbiotic to restore fecal oxalatedegrading activity and ceftriaxone-induced disruption of oxalate homeostasis in rats.Methods Twenty-eight female Wistar rats (200-300 g) were randomly divided into 4 groups (n = 7). Group 1 was treated with vehicle sterile water (0.1 ml, i.m., 14 days); Group 2 received synbiotic (30 mg/kg, per os, 14 days); Group 3 was treated with ceftriaxone (300 mg/kg, i.m., 7 days); Group 4 was supplemented with ceftriaxone and synbiotic. Oxalate-degrading bacteria number and their total activity, urinary and plasma oxalate concentrations were measured on days 1 and 57 after the treatment withdrawal.Results Ceftriaxone treatment reduced total fecal oxalate-degrading activity independently on oxalatedegrading bacteria number and increased urinary and plasma oxalate concentrations. The synbiotic had a high oxalate-degrading activity vs probiotics and was able to restore fecal oxalate-degrading activity and signi cantly decrease urinary oxalate excretion in antibiotic-treated rats.Conclusion Total fecal oxalate-degrading activity but not oxalate-degrading bacteria number should be thoroughly examined in the future to develop predictive diagnostics methods, targeted prevention and personalized treatment in kidney stone disease. Synbiotic supplementation had a bene cial effect on the total oxalate-degrading activity of gut microbiota, which resulted in decreased UOx excretion in rats.

Role of microbiome in kidney stone disease

“…Hence, there is a recent interest in the modulation of the intestinal microbiota through the oral administration of probiotics to influence the initiation and development of kidney stones. In a study with rats treated with ceftriaxone, a synbiotic composed by Lactobacillus acidophilus , Lactobacillus rhamnosus , Lactobacillus plantarum , Lactobacillus casei , Bifidobacterium bifidum , Bifidobacterium longum , Saccharomyces boulardii , oligofructose and inulin restored oxalate-degrading activity and decreased urinary oxalate excretion independently of the number of oxalate-degrading bacteria [27 ▪ ]. In a murine model of hyperoxaluria induced by ethylene glycol, it was also observed that intestinal inflammation and increased intestinal permeability were produced.…”

“…Gut microbiota preferentially uses the oxalate degradation pathway type II, which consists of a two-step reaction involving enzymes such as formyl-CoA transferase and oxalyl-CoA decarboxylase, with coenzyme A as a cofactor [26 ▪▪ ]. Another study in rats has shown that oxalate-degrading activity, but not the number of oxalate-degrading bacteria, should be examined as a diagnostic predictive tool, in prevention and personalized KSD treatment [27 ▪ ]. Another example of the relationship between gut microbiota and the KSD pathogenesis is that in a murine model of induced urolithiasis, administration of a solution with KSD patient feces increased crystal formation and accelerated stone formation [28 ▪ ].…”

Understanding formation processes of calcareous nephrolithiasis in renal interstitium and tubule lumen

“…Based on these findings, manipulating the gut-kidney axis to alleviate hyperoxaluria has emerged as a potentially promising therapeutic approach for patients with CaOx stones. 64 In addition to hypercalciuria and hyperoxaluria, hypocitraturia is strongly associated with stone formation and is present in approximately 20%-60% of patients with calcium stones. [65][66][67] Urinary citrate plays a crucial role in inhibiting the formation of calcium stones by binding with urinary calcium, thereby reducing the concentration of ionized calcium and interfering with calcium crystal nucleation and growth.…”

“…Conversely, rats treated with synbiotics, which promote the growth of beneficial gut microbes, showed a significant decrease urinary oxalate excretion. Based on these findings, manipulating the gut–kidney axis to alleviate hyperoxaluria has emerged as a potentially promising therapeutic approach for patients with CaOx stones 64 …”

Probiotic Oxalate-Degrading Bacteria: New Insight of Environmental Variables and Expression of the oxc and frc Genes on Oxalate Degradation Activity

“…Previous research by Balthazar et al [ 37 ] has shown that among prebiotics, inulin may cause increase survival and activity of LAB during shelf life. Stepanova et al [ 38 ] showed that impact of prebiotics (oligofructose and inulin) on increased degradation of oxalate is due to the increased growth of bacteria resulted from the presence of short chain free fatty acids. Another study by Darilmaz et al [ 39 ] showed that prebiotics could increase the degradation of oxalate by lactobacilli in vitro.…”