Crohn’s-like Gut Inflammation Fuels Kidney Stone Risk in Mice, Study Finds

If you have Crohn's disease or another form of inflammatory bowel disease (IBD) and you have ever passed a kidney stone, you are not imagining a connection. Gastroenterologists have long known that IBD patients face a dramatically higher risk of kidney stones, but the exact mechanism linking a gut problem to a kidney problem has been hard to pin down. A new study in mice, published in the journal Gut Microbes, traces that chain step by step: from a high-fat diet, to a leaky gut, to a shift in gut bacteria, to a buildup of a stone-forming compound in the urine. The model used mimics Crohn's-like inflammation in mice, not human IBD itself, so this maps a mechanism rather than proving it happens the same way in people.

Key takeaways

• In a mouse model of Crohn's-like ileitis (inflammation of the ileum, the last section of the small intestine), a high-fat diet triggered fat malabsorption, a leakier gut, altered gut bacteria, and a buildup of urinary oxalate, a compound that forms kidney stones.
• The inflamed mice developed markers of kidney injury that tracked closely with their oxalate levels, while healthy control mice on the same diet did not show the same pattern.
• IBD patients already carry a 10 to 100 times higher risk of kidney stones than the general population, and this study offers the clearest step-by-step mechanism yet for why.
• This is a mouse study with no human trial and no tested treatment; it maps a pathway, it does not prove a fix.

Ileitis Mice Show a Full Gut-to-Kidney Oxalate Pathway

Researchers found that SAMP1/YitFc mice (an inbred strain that spontaneously develops Crohn's-like inflammation of the ileum) develop enteric hyperoxaluria (abnormally high urinary oxalate caused by excess absorption of oxalate from the gut) when fed a high-fat diet, and that this hyperoxaluria tracked closely with markers of kidney injury. The team fed SAMP1 mice and genetically related AKR control mice, which do not develop ileitis, diets with 10%, 45%, or 60% of calories from fat, all supplemented with oxalate. At the higher fat levels, the inflamed SAMP1 mice excreted significantly more urinary oxalate relative to creatinine than AKR mice, for example 0.45 vs 0.28 micromoles per milligram on the 60% fat diet. Their plasma oxalate was also markedly higher (112 vs 55.7 micromoles per liter on the same diet), and plasma oxalate and plasma creatinine, a marker of kidney function, were strongly correlated in the SAMP1 mice (r = 0.93) but not in the healthy AKR mice (r = 0.32), meaning the oxalate buildup and the kidney strain moved together only when ileitis was present.

Crohn's and IBD Patients Already Face Outsized Kidney Stone Risk

People with Crohn's disease and other inflammatory bowel diseases already carry a 10- to 100-fold higher risk of kidney stones than the general population, with reported stone prevalence in IBD patients reaching as high as 28%. In humans, the leading explanation has been that malabsorbed dietary fat in the small intestine binds to calcium that would otherwise bind oxalate in the gut, leaving more free oxalate to be absorbed into the bloodstream and eventually excreted, and filtered, by the kidneys. This new mouse study is the first to lay out that entire chain, including the gut bacteria piece, in one animal model side by side with a genetically similar strain that does not have ileitis, which lets the researchers separate the effect of inflammation from the effect of diet alone.

Six-Week Diet Trial Compared Ileitis and Healthy Mouse Strains

The researchers fed 11-week-old SAMP1/YitFc mice and AKR controls one of three diets, low-fat (10% of calories from fat), a Western-diet-like high-fat diet (45% fat), or a very-high-fat diet (60% fat), each supplemented with 1% oxalate and a fixed amount of calcium, for six weeks. Every two weeks the mice were housed in metabolic chambers to collect 24-hour urine, and blood was drawn throughout. At the end of the study the researchers analyzed stool lipids with mass spectrometry, directly measured gut permeability using sucralose and labeled oxalate given by gastric gavage, ran gene and protein assays (qPCR and Western blot) on gut and kidney tissue, sequenced the gut microbiome at the community, genus, and functional level, and examined kidney tissue under the microscope for inflammation and immune cell infiltration.

Several findings supported the fat malabsorption piece. SAMP1 stool samples showed elevated diacylglycerols and other lipid classes alongside a trend toward higher free fatty acids, both signs that dietary fat was passing through undigested rather than being absorbed normally. Free fatty acids matter here because they can bind calcium in the gut the same way oxalate does, effectively competing with oxalate for the calcium that would otherwise keep it insoluble and unabsorbed.

The permeability piece was measured directly rather than inferred. SAMP1 mice on the 60% fat diet had significantly lower expression of the tight-junction proteins ZO-1 and occludin in the small intestine, proteins that seal the gaps between intestinal cells and are frequently disrupted in IBD, and their urinary sucralose, a marker of leaky gut, was roughly seven times higher than in AKR mice (22.2% of the dose absorbed versus 3.1%). The gut bacteria piece showed SAMP1 mice consistently had more Bacteroides and Alistipes across all three diets, along with a shift in which bacteria contributed most to oxalate breakdown, and at the highest fat intake, bacterial genetic pathways tied to processing oxalate precursor compounds were altered in ways not seen in the healthy mice. Also on the 60% fat diet, SAMP1 mice had 40% lower expression of SLC26A6, a gut transporter that normally helps secrete excess oxalate back into the intestine for disposal, meaning less oxalate was being cleared even as more of it was getting in.

What This Could Mean If You Have IBD

For someone managing Crohn's disease or another form of IBD, this study is a reminder that dietary fat intake, gut barrier integrity, and gut bacteria composition may all feed into kidney stone risk together, rather than any single factor acting alone. It does not establish that cutting dietary fat will lower stone risk in people, nor does it test any supplement or dietary intervention as a fix, but it does reinforce why enteric hyperoxaluria in IBD is worth taking seriously: unmanaged, it is associated with kidney stones and, over time, progressive kidney damage. If you have IBD and a history of kidney stones, or unexplained kidney function changes, this is a reasonable thing to raise with a gastroenterologist or nephrologist, particularly around periods of active flares or high dietary fat intake, rather than something to self-treat.

Limitations: A Mouse Model, Not Confirmed Human Biology

This is an animal-only study, and SAMP1/YitFc mice model a Crohn's-like ileitis, not the full spectrum of human IBD, which includes ulcerative colitis and colon-predominant Crohn's disease with different anatomy involved. The diets used a fixed, experimentally elevated oxalate supplementation (1%) that does not map directly onto typical human dietary oxalate exposure, and several results, including the trend toward higher intestinal oxalate absorption in SAMP1 mice (25.7% versus 1.9% in AKR), did not reach statistical significance (p = 0.11), meaning it is suggestive but not confirmed. The study also documents that gut bacteria composition differed between the strains without isolating any single bacterial species as causal, so the microbiome's exact contribution, versus simply being a bystander to the permeability and fat malabsorption changes, remains unresolved.

Next Steps: Testing Whether Restoring Specific Gut Bacteria Helps

The researchers found that mice with ileitis relied more heavily on certain bacteria, including Lactobacillus and Muribaculaceae species, for oxalate breakdown, while other oxalate-degrading bacteria, including Bifidobacterium, contributed less compared to healthy mice. That opens an obvious next question: could restoring specific oxalate-degrading bacteria such as Oxalobacter formigenes, which has already been studied as a potential probiotic against kidney stones, reduce hyperoxaluria in an ileitis model, or eventually in IBD patients. That treatment question was not tested here and would require its own dedicated trial. The study was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases and the Rare Kidney Stone Consortium, both of which have an ongoing research interest in enteric hyperoxaluria.

Common Questions

What is enteric hyperoxaluria? It is abnormally high urinary oxalate caused by excess oxalate absorption from the gastrointestinal tract, most often linked to fat malabsorption or a leaky gut, and it is a well-established risk factor for calcium oxalate kidney stones.

Does this mean a high-fat diet causes kidney stones in Crohn's disease? Not on its own. In this mouse study, a high-fat diet alone in healthy control mice did not produce the same degree of hyperoxaluria as it did in mice with ileitis; the inflammation-driven gut permeability and microbiome shift appeared necessary alongside the dietary fat.

Could a probiotic fix this? Not based on this study. It identifies bacteria that differ between ileitis and healthy mice and points to oxalate-degrading species like Oxalobacter formigenes as a research direction, but no probiotic or supplement was tested here as a treatment.

Is this relevant to ulcerative colitis, not just Crohn's disease? This study used a model specific to ileitis, the Crohn's-like pattern of small intestine inflammation, so its findings do not directly speak to ulcerative colitis, which affects the colon rather than the small intestine.

References

1. Nadim Zaidan, Karim Jaber, Melody Ho, et al. (2026). Determinants of enteric hyperoxaluria in the SAMP1/YitFc mouse model of spontaneous ileitis. Gut Microbes. https://doi.org/10.1080/19490976.2026.2725367
2. Roswitha Siener, Charlotte Ernsten, Jan Speller, Christian Scheurlen, Tilman Sauerbruch, Albrecht Hesse (2024). Intestinal Oxalate Absorption, Enteric Hyperoxaluria, and Risk of Urinary Stone Formation in Patients with Crohn’s Disease. Nutrients. https://doi.org/10.3390/nu16020264
3. Biochemical Modulators of Tight Junctions (TJs): Occludin, Claudin-2 and Zonulin as Biomarkers of Intestinal Barrier Leakage in IBD. NIH. https://pmc.ncbi.nlm.nih.gov/articles/PMC11478261/
4. Kidney Stone Events and ESKD Incidence in Patients with Enteric Hyperoxaluria from Diverse Enteric Etiologies. NIH. https://pmc.ncbi.nlm.nih.gov/articles/PMC12889936/
5. David W. Kaufman, Judith P. Kelly, Gary C. Curhan, et al. (2008). Oxalobacter formigenes May Reduce the Risk of Calcium Oxalate Kidney Stones. Journal of the American Society of Nephrology. https://doi.org/10.1681/asn.2007101058