Unraveling the Gut Microbiome's Role in Kidney Stone Formation: Insights from Fecal Microbiota Transplantation Studies

Abstract Emerging research on the microbiome highlights the significant role of gut health in the development of kidney stones, indicating that an imbalance in gut bacteria, or dysbiosis, can influence the formation of stones by altering oxalate metabolism and urinary metabolite profiles. Notably, the presence of specific bacteria such as Enterococcus and Oxalobacter spp., known to affect oxalate absorption, is linked to urolithiasis, prompting further investigation into the gut's role in calcium oxalate stone disease. This study investigates the effects of gut dysbiosis on urolithiasis through fecal microbiota transplantation (FMT) from patients to rats and its impact on urinary mineral excretion and stone formation. Fecal samples from eight patients with calcium oxalate stones and ten healthy volunteers were collected to assess the gut microbiome. These samples were then transplanted into Wistar rats for a duration of four weeks. Post-transplantation, we evaluated changes in the fecal gut microbiome profile, urinary mineral excretion rates, and the expression levels of intestinal zonula occluden-1 (ZO-1), SLC26A6, and renal NF-κB. Patients with urolithiasis exhibited increased levels of urinary calcium and oxalate, alongside decreased citrate excretion and a heightened urinary supersaturation index, with a notable abundance of Bacteroidota. Rats receiving urolithiasis-FMT showed similar disturbances, including elevated urinary oxalate, increased pH, and supersaturation index, despite negative renal pathology. However, significant elevation of the expression of renal NF-κB, intestinal SLC26A6, and a reduction in ZO-1 expression were observed. Additionally, an increased abundance of Bacteroidota, particularly Muribaculaceae, was detected in the feces of urolithiasis rats. Conclusively, the consistent increase in Bacteroidota abundance across both urolithiasis patients and FMT-treated rats is linked to altered intestinal barrier function, hyperoxaluria, and renal inflammation. These findings suggest that gut dysbiosis, characterized by an overgrowth of Bacteroidota, plays a crucial role in the pathogenesis of calcium oxalate urolithiasis, underscoring the potential of targeting gut microbiota as a therapeutic strategy.