Baseline abundance of oxalate-degrading bacteria determines response to Oxalobacter formigenes probiotic therapy

Oxalate, a compound derived from both diet and metabolism, contributes to multiple renal and vascular diseases. Certain gut bacteria degrade oxalate, limiting absorption and promoting secretion. This study examined microbial factors that influence the effectiveness of Oxalobacter formigenes, a specialized oxalate-degrading bacterium, in lowering urinary oxalate levels. We analyzed gut microbiota from a controlled diet study involving 26 healthy, non-stone-forming adults who were initially uncolonized and then colonized with O. formigenes. Stool samples were profiled for 16S rRNA and oxalate-degrading genes-oxalyl-CoA decarboxylase (oxc) and formyl-CoA transferase (frc)-using high-throughput amplicon sequencing and qPCR. Comparative analyses assessed associations between microbial features and oxalate homeostasis, including changes in urinary oxalate excretion. The baseline abundance of oxalate-degrading genes (oxc and frc) was significantly and negatively correlated with stool oxalate (R = -0.43 for frc, -0.34 for oxc), urinary oxalate levels (R = -0.25 for frc, -0.27 for oxc), and the reduction in urine oxalate after O. formigenes administration (R = -0.36 for frc, -0.42 for oxc). This study provides the first direct evidence that baseline oxalate-degrading gene abundance predicts probiotic response. Results explain inconsistent clinical trial results and support precision microbiome-based therapy for hyperoxaluria via targeted patient stratification.