Kidney Week

Abstract: SA-PO686

Analysis of Gut Microbiome Alterations in Hyperoxaluric Patients

Session Information

• Bone and Mineral Metabolism: Clinical - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Nazzal, Lama, New York University School of Medicine, New York, New York, United States

Lama Nazzal,

• Liu, Menghan, New York University School of Medicine, New York, New York, United States

Menghan Liu,

• Seide, Barbara M., Mayo Clinic, Rochester, Minnesota, United States

Barbara M. Seide,

• Mcintosh, Mary, University of Arizona College of Medicine, Tucson, Arizona, United States

Mary Mcintosh,

• Granja, Ignacio, Litholink Corp, Chicago, Illinois, United States

Ignacio Granja,

• Asplin, John R., Litholink Corp, Chicago, Illinois, United States

John R. Asplin,

• Ho, Melody, New York University School of Medicine, New York, New York, United States

Melody Ho,

• Milliner, Dawn S., Mayo Clinic, Rochester, Minnesota, United States

Dawn S. Milliner,

• Goldfarb, David S., New York University School of Medicine, New York, New York, United States

David S. Goldfarb,

• Blaser, Martin J., New York University School of Medicine, New York, New York, United States

Martin J. Blaser,

Group or Team Name

• The Rare Kidney Stone Consortium

Background

About 60–80% of kidney stones are composed of calcium oxalate (CaOx); idiopathic CaOx kidney stones (CaOPx), primary hyperoxaluria (PH) and enteric hyperoxaluria (EH) are diseases predisposing to stones. Oxalobacter formigenes (Oxf) is a human gut commensal that depends on oxalate for its carbon and energy, and may be protective against CaOx stones. We hypothesize that the microbiome community structure differs between patients with CaOx, PH, EH and normal subjects (NS). We also expect that Oxf isolates from PH patients will result in further reduction in urinary oxalate when compared to Oxf reference strain CC13, in a germ-free (GF) mouse model.

Methods

We collected fecal specimens from 34 subjects (mean age: 39.1 + 11.9 years) with PH (n=6), CaOPx (n=10), EH (n= 5) and NS (n=13) in a cross-sectional observational study, and tested fecal samples from the groups by: 1)16S rRNA sequencing to determine the microbiome community structure, 2)PCR and qPCR for Oxf colonization and, 3)culturing in high oxalate selective media for indication of Oxf presence and subsequent isolation. We isolated Oxf from 4 PH (Oxf PH) subjects. We gavaged a growing culture of PH Oxf (n=6), Oxf reference strain CC13 (Oxf CC13) (n=5), and sham (n=6) into adult C5B6 GF mice, observing them for 4 weeks. We collected urine from mice for 48 hours before sacrifice to be tested for oxalate and creatinine (Uox/cr).

Results

Oxf was detected in 6 (46%) of 13 NS, 1 (10%) of 10 CaOPx, 0 (0%)of 4 EH, and 5 (83%) of 6 PH. Microbiome analysis revealed that the 4 groups differed in beta diversity, based on Bray-Curtis dissimilarity (p=0.08). Alpha diversity analysis trended toward lower Shannon and phylogenetic diversity index in the CaOPx and EH subjects compared to PH and NS. Introducing the PH Oxf to GF mice led to lower Uox/cr than in uninoculated controls (0.68 + 0.14, and 2.26 +0.49, respectively, p=0.04 by Mann-Whitney U test), but not significantly different from the Oxf CC13-innoculated mice (0.68 + 0.14, and 0.91 +0.24, respectively, p=0.26 by Mann-Whitney U test).

Conclusion

These studies provide evidence of differences in Oxf colonization rates and in microbiome composition in patients with CaOx stones and show the functional capacity of a PH Oxf strain to ameliorate hyperoxaluria. Studies to expand these patient groups are on-going.

Funding

• NIDDK Support