Calcium Oxalate Urolithiasis: A Case of Missing Microbes?

Introduction: Urinary stone disease (USD) has known associations with the gut microbiota. Approximately 80% of kidney stones contain oxalate as a primary constituent and diverse oxalate-degrading bacteria exist within the human gut, which may protect against USD. Although bacteriotherapy represents a promising strategy to eliminate oxalate and reduce the risk of USD, oxalate-degrading probiotics have had limited success. To identify limitations of oxalate-degrading probiotics and refine development of bacteriotherapies to prevent USD, we review the literature associated with the gut microbiota and USD. Materials and Methods: A literature search was performed to identify publications that examine the role of oxalate-degrading bacteria or the whole gut microbiota in oxalate metabolism and the pathophysiology of USD. We conducted a meta-analysis of studies that examined the association of the whole gut microbiota with USD. In addition, we evaluated the gut microbiota of healthy individuals and those with comorbidities related to USD using publically available data from the American Gut Project (AGP). Results: Studies on Oxalobacter formigenes reveal that colonization by this species is not a good predictor of USD risk or urinary oxalate excretion. The species of oxalate-degrading bacteria used in probiotics and duration of administration do not impact efficacy or persistence. Studies focused on the whole gut microbiota reveal broad shifts in the gut microbiota associated with USD and a diverse microbial network is associated with oxalate metabolism. AGP data analysis demonstrated a strong overlap in microbial genera depleted in diseased individuals among USD and comorbidities. Conclusions: The associations between the gut microbiota and USD extend beyond individual functional microbial species. Common shifts in the gut microbiota may facilitate the onset of USD and/or comorbidities. The successful development of bacteriotherapies to inhibit USD will need to incorporate strategies that target a broad diversity of bacteria rather than focus on a few specialist species.