Abstract: FR-PO232
Enteric Hyperoxaluria Mouse Model: Malabsorption and Gut Permeability
Session Information
- Mineral Bone Disease: Transplant and Kidney Stones
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
Authors
- Jaber, Karim, NYU Langone Health, New York, New York, United States
- Zaidan, Nadim, Staten Island University Hospital, Staten Island, New York, United States
- Merritts, Kyle, NYU Langone Health, New York, New York, United States
- Xiong, Xiaozhong, NYU Langone Health, New York, New York, United States
- Nazzal, Lama, NYU Langone Health, New York, New York, United States
Background
Enteric hyperoxaluria (EH) arises from enhanced oxalate (Ox) absorption in the gastrointestinal (GI) tract, often seen in patients with inflammatory bowel diseases. Several mechanisms could contribute to this, including elevated Ox bioavailability, decreased fat absorption, and altered GI permeability. The SAMP1/YitFc (SAMP1) mouse model exhibits spontaneous ileal inflammation resembling Crohn’s disease. We hypothesize that SAMP1 mice exhibit increased gut permeability and develop an EH phenotype.
Methods
To assess intestinal permeability, we performed gavage of 10 AKR and 10 SAMP1 mice (1:1 F:M) with sucralose and C-13 Ox at weeks 16, 20, and 26 of life. We collected 24-hour urine post-gavage and measured sucralose via Hydrophilic Interaction Liquid Chromatography (HILIC).
To evaluate the impact of ileitis and dietary fat, SAMP1 and AKR mice (n=10/group) were initially fed normal chow before transitioning to a low-fat diet, then a very high-fat diet. Ox was then introduced with incremental decrease in dietary fat. Urine (U) and plasma (P) samples were collected for Ox and creatinine measurements, and fecal samples were collected for Ox and lipidomics analysis to investigate fat malabsorption.
Results
SAMP1 mice had higher % of sucralose absorption, suggesting increased intestinal permeability in IBD mice.
Increased dietary fat did not induce increase in UOx. However, dietary oxalate addition to fat led to an increase in UOx, POx and fecal oxalate. Fecal lipidomics indicated increased lipids, particularly fatty acids, in SAMP1 mice confirming fat malabsorption.
Conclusion
SAMP1 mice develop an EH phenotype characterized by increased fat malabsorption, leading to elevated dietary Ox bioavailability. These mice had increased gut permeability, likely promoting passive oxalate absorption across the intestinal membrane.