Hidden Compound in Healthy Foods Worsens IBD

Transporter Proteins and Oxalate Absorption in IBD

The study, led by postdoctoral scholar Anna Salvador, PhD, RD, LDN, in the lab of Shehzad Z. Sheikh, MD, PhD, investigated why oxalate processing fails in compromised intestines. Researchers examined gene activity, stool oxalate levels, and dietary patterns in individuals with and without IBD, alongside experiments involving mice and cultured cells. According to the findings, two specific transporter proteins responsible for moving oxalate out of the gut—SLC26A2 and SLC26A3—appear at consistently lower levels in intestinal tissue from patients suffering from both ulcerative colitis and Crohn’s disease. This reduction occurs across affected tissues regardless of active inflammation, and lower transporter expression correlates with increased tissue inflammation. When these biological transport systems fail, less dietary oxalate is absorbed, leaving excess oxalate behind to amplify intestinal inflammation.

DNA Metabarcoding Reveals Crohn’s Disease Discrepancies

Using a validated dietary questionnaire (Diet History Questionnaire III) alongside DNA metabarcoding to detect plant species in stool samples, the research team discovered a striking divergence in Crohn’s disease patients. People with Crohn’s disease harbored significantly higher levels of oxalate in their stool than healthy control subjects, despite both groups consuming equivalent amounts of plant-based foods. According to Dr. Salvador, this marked the first deployment of DNA metabarcoding 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,” Dr. Salvador stated. This discrepancy underscores that elevated intestinal oxalate stems from a fundamental processing flaw in the gut rather than dietary intake alone.

Animal Models and Immune Cell Responses

To test these mechanisms, the research team conducted multiple animal and cellular experiments. Mice placed on an oxalate-supplemented diet alongside a colitis-inducing substance experienced a 60 percent drop in survival compared to mice receiving no extra dietary oxalate. Furthermore, in two separate mouse models genetically predisposed to spontaneous colitis, dietary oxalate accelerated disease onset and severity. Notably, genes responsible for oxalate transport showed reduced activity in these susceptible mice even before dietary oxalate was introduced, mirroring the pattern documented in human IBD tissue. In cell culture experiments, oxalate intensified inflammatory responses within macrophages and dendritic cells, which are key immune regulators of the intestinal lining.

Implications for Stricturing Crohn’s Disease

The study also explored potential genetic markers for disease progression. In an exploratory analysis, low expression of an additional transporter called SLC26A6 linked directly to stricturing Crohn’s disease, an aggressive form of the condition characterized by scar tissue buildup and intestinal narrowing. Nearly 75 percent of patients exhibiting low SLC26A6 expression suffered from stricturing disease. While this points toward a potential prognostic tool for identifying high-risk patients, the authors emphasize that larger patient cohorts are required to confirm the association. “Dr. Salvador really conceptualized and drove this work from the beginning,” said Dr. Sheikh, highlighting her approach to viewing a dietary molecule as an active driver rather than a passive bystander in gut inflammation.

Frequently Asked Questions

Should people with IBD completely stop eating plant foods like spinach and almonds?

No. The researchers emphasize that the findings do not suggest patients should eliminate healthy plant-based foods from their diets, as it remains entirely possible to follow a nutritionally complete plant-based diet while moderating total oxalate exposure.

What causes elevated oxalate levels in IBD patients?

According to the UNC School of Medicine study, elevated oxalate is driven primarily by a biological impairment in how the gut handles the compound, specifically due to lower levels of SLC26A2 and SLC26A3 transporter proteins in the intestinal tissue.

Are there official new dietary guidelines for IBD and oxalate?

Not yet. Researchers caution that the current findings are insufficient to establish formal clinical recommendations regarding oxalate intake, and future longitudinal studies involving larger patient groups are necessary before guidelines change.