Spontaneous ileitis and postsurgical murine models of enteric hyperoxaluria.

Enteric hyperoxaluria, a risk factor for kidney stone disease, often arises from malabsorptive bariatric surgeries or inflammatory bowel diseases. Current murine models for studying this condition are limited, necessitating new approaches. This study aims to establish two novel and distinct mouse models to investigate enteric hyperoxaluria: one simulating Roux-en-Y gastric bypass surgery and the other Crohn's ileitis. In the first model, diet-induced obese C57BL/6J male mice underwent either sham or bypass surgery, followed by 3 wk on a high-fat, oxalate-enriched diet. In the second model, SAMP1/YitFc and AKR mice were gradually introduced to high-fat diets, later supplemented with oxalate while reducing fat content. Samples of urine, blood, and feces were collected to assess oxalate, creatinine, and fecal lipid profiles. Results showed hyperoxaluria and increased stool fat content, indicating fat malabsorption, in both SAMP1 and bypass mice compared with controls. Kidney injury was also observed. These findings confirm the successful establishment of enteric hyperoxaluria in both models, highlighting the role of dietary oxalate, intestinal inflammation, and fat malabsorption in disease progression. These models provide valuable tools for exploring cellular and molecular mechanisms in enteric hyperoxaluria and may inform future therapeutic strategies.NEW & NOTEWORTHY This study is among the first to establish an enteric hyperoxaluria (EH) phenotype in two different and novel mouse models secondary to Roux-en-Y gastric bypass and ileitis. It also elucidates key factors affecting EH using the SAMP1 mice, revealing the significant roles of GI tract inflammation, fat malabsorption, and dietary fat in developing hyperoxaluria.