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Colonization with Oxalobacter formigenes slows the progression of CKD and reduces cardiac remodeling in CKD
Xiaozhong Xiong1, Melody Ho1, Karim Jaber1
1Division of Nephrology, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA.
Insights
Reducing oxalate levels by colonizing the gut with Oxalobacter formigenes (Oxf) may slow chronic kidney disease (CKD) progression and prevent heart complications in CKD patients.
Area of Science:
- Nephrology
- Cardiology
- Microbiology
Background:
- Oxalate accumulation in chronic kidney disease (CKD) is linked to disease progression and cardiac mortality.
- The potential of reducing oxalate to slow CKD and prevent cardiovascular issues is unknown.
Purpose of the Study:
- To investigate the therapeutic potential of gut microbiota-mediated oxalate degradation in mitigating CKD and associated cardiovascular complications.
Main Methods:
- Mice with induced CKD were colonized with Oxalobacter formigenes (Oxf), an oxalate-degrading bacterium.
- Mice were fed hydroxyproline (an oxalate precursor) for 23 weeks, followed by assessment of kidney and heart pathology.
- RNA sequencing analyzed metabolic pathway changes in cardiac tissue.
Main Results:
- Oxf colonization significantly reduced plasma oxalate and creatinine levels in CKD mice.
- Kidney inflammation and fibrosis were mitigated, and cardiac remodeling was reduced.
- Oxf reversed CKD-associated dysregulation of metabolic pathways in ventricular tissue.
Conclusions:
- Oxalate accumulation contributes to both CKD progression and cardiovascular complications.
- Targeting plasma oxalate reduction, potentially via microbial interventions like Oxf, may offer therapeutic benefits for CKD patients.
Abstract:
Accumulation of oxalate in patients with chronic kidney disease (CKD) is associated with CKD progression and increased risk of cardiac death. Whether reducing plasma or urine oxalate slows CKD progression and prevents cardiovascular complications remains unexplored. We colonized the intestines of control and CKD mice with Oxalobacter formigenes (Oxf), an oxalate-degrading microorganism. The mice were fed with the oxalate precursor hydroxyproline for 23 weeks at which time we assessed pathological changes in the kidney and heart. We demonstrate that Oxf reduces plasma oxalate (pOx) and creatinine levels, mitigates inflammation and fibrosis in the kidney, and reduces pathologic cardiac remodeling in the hearts of CKD mice. RNA-seq analysis of ventricular tissue of CKD mice reveals dysregulated expression of metabolic pathways while Oxf colonization reverses these changes. These findings demonstrate that oxalate accumulation plays a role not only in CKD progression but also in associated cardiovascular complications and suggest that strategies to reduce plasma oxalate levels may have therapeutic benefit.
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