Spinach, almonds and sweet potatoes are often praised for their nutritional value. But new research from the UNC School of Medicine suggests that for people with inflammatory bowel disease (IBD), a natural compound in these foods may contribute to intestinal inflammation.
The study, published on August 13, 2026 in Gastroenterology and Cellular and Molecular Hepatology (CMGH), was led by postdoctoral researcher Anna Salvador, PhD, RD, LDN, in the laboratory of Shehzad Z. Sheikh, MD, PhD, professor of Medicine and Genetics.
The researchers examined gene activity, fecal oxalate levels, and dietary patterns in people with IBD and in people without the disease. They also conducted experiments in mice and cell cultures to investigate how dietary oxalate could influence inflammation of the intestinal lining.
IBD can impair the intestine’s ability to handle oxalate
Oxalate is a natural compound found in all plant foods. Even in a healthy digestive system, most dietary oxalate passes through the body and is eliminated in the feces.
However, the researchers found that two transporter proteins involved in moving oxalate out of the intestine, SLC26A2 and SLC26A3, were consistently present at lower levels in the intestinal tissue of patients with ulcerative colitis and Crohn’s disease.
This reduction appeared in all affected tissues regardless of whether there was active inflammation. The researchers also found that the more inflamed the tissue, the lower the expression of these transporters tended to be.
When these transport systems are impaired, less oxalate is absorbed from the diet. That leaves more oxalate in the gut environment, where new findings suggest it may amplify the inflammation already associated with IBD.
Crohn’s patients had more oxalate despite similar diets
One of the most surprising findings involved people with Crohn’s disease. They had significantly higher levels of oxalate in their stool than people without IBD, even though the two groups regularly consumed similar amounts of plant-based foods.
The researchers reached that conclusion using two separate approaches. One was a validated dietary questionnaire (Diet History Questionnaire III). The other was DNA metabarcoding, a molecular method that detects plant species represented in stool samples.
According to the researchers, this is the first time that DNA barcoding has been used to assess diet in an IBD population.
“For the first time, we observed that IBD patients and healthy controls ate similar amounts of plant-based foods, but CD patients still had more oxalate in their stool,” Dr. Salvador said. “That told us that it’s not just about what patients eat. There’s something fundamentally different about the way their gut handles oxalate.”
The result suggests that elevated oxalate in the intestines may be due less to the amount of oxalate a person ingests and more to a biological problem in the way the intestine processes it.
Animal experiments strengthen the bond
The researchers also tested the effects of oxalate in several animal models.
Mice given a diet supplemented with oxalate along with a colitis-inducing substance were 60 percent less likely to survive than mice given no additional oxalate in the diet.
In two separate mouse models genetically prone to developing spontaneous colitis, dietary oxalate also caused the disease to appear earlier and become more severe.
Importantly, the genes responsible for oxalate transport were already less active in these susceptible mice before oxalate was added to their diets. That pattern closely resembled what researchers observed in people with IBD.
Experiments with cell cultures produced another clue. Oxalate intensified inflammatory responses in macrophages and dendritic cells, immune cells that play important roles in protecting and regulating the intestine.
A possible marker for more severe Crohn’s disease
The team also explored whether oxalate-related genes could provide clues about how Crohn’s disease progresses.
In an exploratory analysis, low expression of another transporter called SLC26A6 was associated with Crohn’s disease stenosis. This is a more aggressive form of the condition in which scar tissue builds up, causing parts of the intestine to narrow.
Nearly 75 percent of patients with low SLC26A6 expression had stenosing disease.
That raises the possibility that oxalate transporter activity could eventually help doctors identify patients at higher risk of developing more severe disease. However, the researchers emphasize that the finding needs to be confirmed in larger groups of patients.
“Dr. Salvador really conceptualized and drove this work from the beginning,” Dr. Sheikh said. “He asked a question that hadn’t been asked before: What if a specific dietary molecule is an active driver of intestinal inflammation in IBD, and not just a bystander? The rigor he brought to answering is what makes these findings so compelling.”
What the findings mean for people with IBD
The results do not suggest that people with IBD should eliminate plant foods from their diet.
Instead, the findings indicate that in genetically susceptible people, even moderate amounts of oxalate can contribute to inflammation of the intestinal lining. The researchers also suggest that previous studies on diet and IBD may have been complicated by differences in how individual patients are exposed to or process oxalate.
It is still possible to follow a nutritionally complete plant-based diet while reducing overall oxalate intake.
The gut microbiome could also provide another avenue for treatment. Certain intestinal bacteria, including Oxalobacter formigenescan break down oxalate. These bacteria are less abundant in people with IBD.
This raises the possibility that future microbiome-based treatments could improve oxalate breakdown within the gut, potentially offering an alternative to relying solely on dietary restriction.
More research needed before dietary guidelines change
The researchers caution that the findings are not yet enough to support formal recommendations on oxalate intake for people with IBD.
Future studies will need to follow larger groups of patients over time while combining stool oxalate measurements, carefully documented dietary intake, molecular profiling, and microbiome analysis.
“For patients living with Crohn’s disease or ulcerative colitis, this research opens up a genuinely new therapeutic angle that connects the food on your plate to the inflammation in your gut,” Dr. Sheikh said. “Diet is one of the most powerful modifiable levers we have in medicine, and this study gives us a molecular framework to begin using it more precisely.”
The study was supported by the Helmsley Charitable Trust, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the Chan Zuckerberg Initiative, Schmidt Sciences, the Burroughs Wellcome Fund, and additional sources from the National Institutes of Health. Co-authors span UNC-Chapel Hill, Texas A&M University and Duke University.