Probiotic and Synbiotic Interventions Targeting Oxalate-Degrading Gut Bacteria for the Prevention of Kidney Stones: A Systematic Review.

Kidney stone disease (KSD) is a common and recurrent healthcare problem. Calcium oxalate stones are the most common type of stones, influenced by urinary oxalate levels. Increasingly, the role of the gut microbiome is being studied, particularly oxalate-degrading bacteria such as Oxalobacter formigenes, Lactobacillus, and Bifidobacterium, as potential therapeutic targets. Probiotic and synbiotic interventions aimed at enhancing intestinal oxalate degradation have, therefore, been proposed as strategies to reduce urinary oxalate excretion and mitigate stone recurrence.  A comprehensive search of PUBMED, Cochrane Library, Scopus, and Embase databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of nine studies, published between January 1, 2000, and September 3, 2025, met the inclusion criteria, comprising five randomized controlled trials and four observational studies. Interventions included O. formigenes preparations, lactic acid bacteria mixtures, and multi-strain probiotics or synbiotics. Urinary oxalate excretion was the most consistently reported outcome, while assessment of kidney stone recurrence was limited due to short study durations and follow-ups.  Across trials, probiotic or synbiotic therapy did not consistently reduce urinary oxalate levels compared with placebo or standard care. Although several studies demonstrated successful gastrointestinal colonization with O. formigenes, this did not translate into meaningful biochemical improvements. One randomized trial reported a reduction in the incidence of hyperoxaluria compared with an active comparator; however, this finding was not replicated elsewhere, and no included study demonstrated a significant reduction in clinically confirmed stone recurrence. Overall, the quality of evidence was limited by small sample sizes, heterogeneity in probiotic strains, dosing regimens, and short intervention periods.  Current evidence does not support the use of probiotics or synbiotics targeting oxalate-degrading bacteria as effective therapies for reducing urinary oxalate excretion or preventing kidney stone recurrence. Despite their biological plausibility and favourable safety profile, their clinical utility remains unproven. Future research should prioritize long-term, randomized trials using standardized microbial formulations and incorporating imaging-confirmed recurrence outcomes to more definitively establish the role of microbiome-based interventions in KSD prevention.