Plant Compound Oxalate May Trigger Gut Inflammation in IBD Patients

Spinach, beetroot, almonds, and sweet potatoes are among the foods most often recommended for their nutritional density. They're staples of plant-based diets, celebrated by nutritionists and health advocates. But for people living with inflammatory bowel disease, a new study from the University of North Carolina suggests these same foods may be quietly fueling the inflammation that defines their condition—not because of what they contain in the obvious sense, but because of a compound called oxalate that their bodies cannot process the way healthy bodies do.

Oxalate is present in all plant-based foods. It serves no known function in human metabolism; we simply excrete most of it as waste. For most people, this is unremarkable. But researchers led by gastrointestinal biologist Anna Salvador discovered something unexpected when they measured oxalate intake against oxalate levels in stool samples from 46 participants, some with Crohn's disease and some without. Patients with Crohn's disease and healthy controls were eating similar amounts of plant-based foods, yet the Crohn's patients retained significantly more oxalate in their digestive systems. The difference wasn't about diet. It was about biology.

The team examined genes responsible for producing transporter proteins called SLC26A2 and SLC26A3, which pull oxalate from the gut and move it out of the body. In tissue samples from hundreds of people with Crohn's disease, ulcerative colitis, and healthy controls, these genes were substantially less active in the IBD patients. The genetic machinery that should have been clearing oxalate was running at reduced capacity. In a separate analysis of 131 people with Crohn's disease, a third transporter protein, SLC26A6, showed the same pattern: less active genes correlated with more severe disease.

To understand what happens when oxalate accumulates, the researchers conducted experiments on mice with deliberately inflamed guts designed to mimic IBD. Animals given extra oxalate fared worse across multiple measures: they lost more weight, developed more intense intestinal inflammation that persisted longer, and had lower survival rates. When the team tested how mouse immune cells responded to oxalate in laboratory conditions, the compound triggered an amplified inflammatory response. This suggested that oxalate wasn't causing direct physical damage to the gut lining—instead, it was triggering an immune system reaction in susceptible individuals.

The findings open a new angle for treatment. Rather than asking patients to eliminate nutrient-dense plant foods, researchers are considering ways to improve how the body processes oxalate. One approach would target the transporter proteins directly, essentially restoring the biological machinery that should be clearing the compound. Another possibility involves supplements—potentially probiotics or other interventions—that could help the body eliminate oxalate more efficiently. Geneticist Shehzad Sheikh, also from the University of North Carolina, framed the discovery as a bridge between two domains that are often treated separately: the food on a patient's plate and the inflammation in their gut.

The researchers emphasize that these findings do not mean people with IBD should avoid spinach or beetroot. Rather, moderating oxalate intake could reduce symptoms for those whose bodies struggle to process it. The work also underscores how much variation exists between individuals in how they metabolize the same foods. Larger studies will be needed to identify which patients are most sensitive to oxalate and to test whether the proposed interventions actually work. But for people living with Crohn's disease or ulcerative colitis, the research offers something that has been scarce: a molecular explanation for why certain foods trigger their symptoms, and a concrete target for future treatment.