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Abstract: FR-PO531

The Role of the Microbiota in Mammalian Oxalate Metabolism

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Nazzal, Lama, New York University School of Medicine, New York, New York, United States
  • Liu, Menghan, New York University School of Medicine, New York, New York, United States
  • Ho, Melody, New York University School of Medicine, New York, New York, United States
  • Granja, Ignacio, Litholink Corporation, Chicago, Illinois, United States
  • Asplin, John R., Litholink Corporation, Chicago, Illinois, United States
  • Goldfarb, David S., New York University School of Medicine, New York, New York, United States
  • Blaser, Martin J., New York University School of Medicine, New York, New York, United States
Background

Kidney stones represent a disease of worldwide prevalence with significant public health implications. About 60–80% of stones are composed of calcium oxalate (CaOx); hyperoxaluria is a major risk factor for CaOx stones. Oxalate is an end-product of mammalian digestion and as with urea, must be excreted. We obtain oxalate from diet, or from endogenous production. Certain intestinal bacteria have the ability to degrade oxalate, protecting against oxalate nephropathy, including nephrolithiasis. To understand the role of the gut microbiome in oxalate metabolism, we compared conventional mice with germ-free mice (that lack a microbiota). In addition to the stress of endogenous oxalate production, we challenged groups with dietary and metabolic (via hydroxyproline (Hyp)supplementation) oxalate loads.

Methods

Conventional (CO) and germ-free (GF) mice were fed normal chow diets supplemented with either 1% Oxalate (Ox), 1% Hydroxyproline (Hyp) or were unsupplemented (NC) for 6 weeks (n=3-4/mice group). After 6 weeks, we obtained 48-hour urine collections for measurement of the oxalate/creatinine ratio (Uox/cr).

Results

In CO mice, Uox/cr increased with the Ox diet compared with NC (0.57 + 0.17 vs 0.16 + 0.05, p= 0.03 by Student’s t test), but not with the Hyp diet (0.14 +0.03 vs 0.16 +0.05, p=ns). However, in germ-free mice, both dietary Hyp and Ox led to increased Uox/cr compared to NC diet (0.50 + 0.04, 0.85 + 0.11, vs. 0.31+ 0.06, p<0.05 by ANOVA, respectively). Uox/Cr was lower in CO mice than GF mice when receiving Hyp (p=0.01, by Student’s t test), Ox (p=0.06), and NC diets (0.06).

Conclusion

In conclusion, oxalate excretion was higher in the germ-free than in the conventional mice under all three dietary conditions (Ox, Hyp, NC), providing direct evidence that the normal gut microbiome plays a protective (symbiotic) role in oxalate metabolism. With the metabolic stress of the Hyp diet, the CO mice but not the germ-free mice could compensate. Since mice are not colonized with O. formigenes, this work indicates that other members of their microbiota have the functional capacity to alter oxalate metabolism.

Funding

  • NIDDK Support