Oxalobacter formigenes colonization slows the progression of CKD and reduces cardiac remodeling in CKD

Accumulation of oxalate in patients with chronic kidney disease (CKD) is associated with CKD progression and an increased risk of cardiac death. Whether reducing oxalate slows CKD progression and prevents cardiovascular complications remains unexplored. We colonized Oxalobacter formigenes (Oxf), an oxalate-degrading microbiome, in the intestines of control and CKD mice fed with 1% hydroxyproline for 23 weeks. RNA-seq analysis of heart tissues of CKD mice reveals dysregulated expression of metabolic pathways and Oxf colonization reverses these changes. These findings demonstrate that oxalate accumulation plays a role not only in CKD progression but also in cardiovascular complications. Male C57BL/6 adult mice (40) were purchased from Jackson Laboratories (Bar Harbor, ME). At 6 weeks of age, half underwent two-stage 5/6 nephrectomy (5/6 Nx) surgery, entailing the removal of two-thirds left kidney followed by a right nephrectomy within one week, to induce CKD. The remaining 20 mice underwent sham operations and served as controls. Mice were fed a diet supplemented with 1% hydroxyproline and 0.5% calcium for the duration of the experiment. On day 7, the CKD and sham groups were orally gavaged with either one dose of Oxf (1x109 CFU in 200µl culture medium) or vehicle (V, 200µl culture medium), resulting in four groups of 10 mice each: CKD+Oxf, sham+Oxf, CKD+V and sham+V