A natural compound found in plant-based foods like spinach, almonds, and sweet potatoes may worsen intestinal inflammation in people with inflammatory bowel disease (IBD), according to a study led by researchers at the University of North Carolina at Chapel Hill. The findings, published in the journal Cellular and Molecular Gastroenterology and Hepatology, suggest that individuals with Crohn’s disease and ulcerative colitis may process oxalate—this compound—differently, leading to increased gut inflammation. Oxalate is a naturally occurring substance in plant foods. In a healthy digestive system, most of it is removed from the body through stool. However, researchers found that two key proteins involved in removing oxalate from the gut, SLC26A2 and SLC26A3, were consistently found at lower levels in the intestinal tissue of IBD patients. This reduction was observed in affected tissues regardless of whether active inflammation was present. The study also noted that as inflammation worsened, the levels of these transporters tended to drop further. To investigate the role of diet, the researchers used a validated dietary questionnaire and DNA metabarcoding, a technique that identifies the types of food consumed based on genetic material in stool samples. They found that individuals with Crohn’s disease had significantly higher levels of oxalate in their stool compared to those without IBD, despite similar diets. This suggests that differences in how the gut processes oxalate—not just how much is consumed—may contribute to higher oxalate levels in IBD patients. Animal experiments supported the link between dietary oxalate and intestinal inflammation. Mice given an oxalate-rich diet along with a substance that induces colitis were 60% less likely to survive compared to those not given extra oxalate. In genetically susceptible mouse models, dietary oxalate caused colitis to develop earlier and become more severe. These mice already had lower activity in the genes responsible for oxalate transport before oxalate was added to their diets, a pattern similar to that seen in human IBD patients. In cell culture experiments, oxalate was found to increase inflammation in immune cells like macrophages and dendritic cells, which are crucial for gut health. The study also found that lower levels of another transporter called SLC26A6 were linked to stricturing Crohn’s disease, a more severe form of the condition. Nearly 75% of patients with reduced SLC26A6 expression had this aggressive form of the disease, suggesting that transporter activity could help identify those at higher risk. The researchers emphasize that the findings are not yet enough to make formal recommendations about oxalate intake for people with IBD. Future research will need to follow larger groups of patients over time, combining data on stool oxalate levels, dietary intake, molecular profiles, and gut microbiome composition. The study also highlights the potential for microbiome-based treatments to improve oxalate breakdown, as certain gut bacteria, including Oxalobacter formigenes, are less common in IBD patients. While people with IBD should not eliminate plant-based foods, those who are genetically susceptible may need to consider reducing their oxalate intake.