Hidden oxalate in healthy foods may worsen IBD through impaired gut transport

Spinach, almonds, and sweet potatoes are foods most people consider unambiguously healthy. But for people living with Crohn's disease or ulcerative colitis, a natural compound present in these same foods may be quietly amplifying the inflammation that defines their condition. The culprit is oxalate, a molecule found in all plant foods that the human body normally processes without incident. New research suggests that in people with inflammatory bowel disease, something goes wrong in that process—and the consequences may be more significant than anyone previously understood.

A team led by postdoctoral researcher Anna Salvador at the University of North Carolina examined gene activity, stool samples, and eating patterns in both people with IBD and healthy controls. They also ran experiments in mice and cultured immune cells to trace how oxalate might drive intestinal inflammation. What they found, published in August 2026 in Cellular and Molecular Gastroenterology and Hepatology, points to a specific biological failure: two transporter proteins responsible for moving oxalate out of the gut—SLC26A2 and SLC26A3—appear consistently diminished in the intestinal tissue of people with both ulcerative colitis and Crohn's disease. This reduction held true whether the tissue was actively inflamed or not, and it worsened as inflammation increased. When these transporters are compromised, less oxalate gets absorbed and more accumulates in the intestinal environment, where it appears to intensify the inflammatory cascade already underway.

One of the study's most striking findings emerged when researchers compared what people with Crohn's disease were actually eating to what they were excreting. Using both a validated dietary questionnaire and a molecular technique called DNA metabarcoding—which identifies plant species in stool samples—the team discovered that Crohn's patients had significantly higher levels of oxalate in their stool than healthy people, despite consuming similar amounts of plant-based foods. This was the first time DNA metabarcoding had been used to evaluate diet in an IBD population. "For the first time, we observed that IBD patients and healthy controls were eating similar amounts of plant-based foods yet CD patients still had more oxalate in their stool," Salvador said. The implication was clear: the problem was not how much oxalate people were eating, but how their bodies were handling it.

To test whether oxalate itself could worsen IBD, the researchers turned to animal models. Mice given an oxalate-supplemented diet alongside a substance that triggers colitis were 60 percent less likely to survive than mice receiving only the colitis trigger. In two separate mouse strains genetically predisposed to spontaneous colitis, adding dietary oxalate made the disease appear sooner and progress more severely. Notably, these susceptible mice already had reduced activity in their oxalate-transport genes before any dietary oxalate was introduced—a pattern that mirrored what the researchers had observed in human IBD patients. In cell culture experiments, oxalate intensified inflammatory responses in macrophages and dendritic cells, immune cells central to intestinal protection and regulation.

The research also hinted at a possible clinical application. In an exploratory analysis, low expression of a third transporter protein, SLC26A6, was associated with stricturing Crohn's disease—a more aggressive form of the condition in which scar tissue narrows the intestine. Nearly 75 percent of patients with low SLC26A6 expression had stricturing disease. While the researchers emphasize this finding requires confirmation in larger patient groups, it raises the possibility that oxalate-transporter activity could eventually help identify people at higher risk of severe progression.

The findings do not argue for eliminating plant foods from the diets of people with IBD. Instead, they suggest that in genetically susceptible individuals, even moderate oxalate intake may contribute to intestinal inflammation. The research also implies that previous dietary studies in IBD populations may have been confounded by unmeasured differences in how individual patients process oxalate. A nutritionally complete plant-based diet can still be achieved while reducing total oxalate consumption. Another avenue lies in the microbiome: certain bacteria, including Oxalobacter formigenes, can break down oxalate in the gut, and these bacteria are less abundant in people with IBD. Future microbiome-based treatments might improve oxalate breakdown, offering an alternative to dietary restriction alone.

The researchers are careful to note that these findings are not yet sufficient to support formal dietary guidelines for IBD patients. Larger, longer studies combining stool oxalate measurements, detailed dietary tracking, molecular profiling, and microbiome analysis will be necessary before clinical recommendations change. But the work has opened what Shehzad Sheikh, the lab's principal investigator, calls "a genuinely new therapeutic angle"—one that connects the food on a patient's plate to the inflammation in their gut through a specific molecular mechanism. For people managing Crohn's disease or ulcerative colitis, the implication is that diet may soon become a more precise tool in their treatment arsenal, tailored not just to general nutrition but to how their individual biology processes what they eat.