Oxalate in spinach and almonds may worsen gut inflammation in IBD

Spinach, almonds and sweet potatoes are celebrated as some of the healthiest foods on the planet. But for the millions of Americans living with inflammatory bowel disease (IBD), a new study from the UNC School of Medicine suggests that these same foods may be quietly worsening gut inflammation through a compound most people have never heard of.

Published in Cellular and Molecular Gastroenterology and Hepatology (CMGH), the study was led by postdoctoral scholar Anna Salvador, Ph.D., RD, LDN, in the lab of Shehzad Z. Sheikh, MD, Ph.D., professor of medicine and genetics.

The team measured gene expression, stool oxalate content and dietary intake in IBD patients and controls and conducted complementary experiments in mouse models and cell culture systems to evaluate how dietary oxalate relates to mucosal inflammation in IBD.

The gut’s oxalate machinery is broken in IBD

Oxalate is a naturally occurring compound present in all plant foods. Most dietary oxalate is eliminated in the stool, even in the healthy gut. However, the study found that specialized transporter proteins responsible for the absorption of oxalate from the gut, SLC26A2 and SLC26A3, are consistently and significantly reduced in gut tissue from patients with both ulcerative colitis and Crohn’s disease, across affected tissues and irrespective of inflammation status. The more inflamed the tissue, the lower the transporter expression.

When these transporters are impaired, dietary oxalate is not properly absorbed, leaving more of it to accumulate in the intestinal environment, where the study’s data suggest it amplifies the very inflammation that defines IBD.

A dietary paradox—and a methodological first

Crohn’s disease patients had significantly higher stool oxalate levels than non-IBD controls, even though both groups habitually consume similar amounts of plant-based foods.

This was confirmed using two independent dietary measures: a validated dietary questionnaire (Diet History Questionnaire III) and DNA metabarcoding, a molecular technique that identifies plant species present in stool samples. This is the first time metabarcoding has been used to assess 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 Crohn’s disease patients still had more oxalate in their stool,” Salvador said. “That told us this isn’t just about what patients eat. Something is fundamentally different about how their gut handles oxalate.”

The finding points to a biological defect in oxalate handling, rather than simply how much oxalate a patient consumes, as the key driver of elevated intestinal oxalate in IBD.

Mouse models reinforce the human signal

The human findings were reinforced in controlled animal experiments. Mice fed an oxalate-supplemented diet alongside a colitis-inducing agent were 60% less likely to survive than those not receiving dietary oxalate. In two independent, genetically susceptible mouse models of spontaneous colitis, dietary oxalate accelerated disease onset and worsened severity.

Critically, the oxalate transporter genes were already reduced at baseline in these susceptible models before dietary oxalate was introduced, mirroring the pattern seen in human IBD patients. In cell culture experiments, oxalate exaggerated inflammatory responses in macrophages and dendritic cells, key players in intestinal immune defense.

A potential signal for disease trajectory

In an exploratory analysis, low expression of a third transporter, SLC26A6, was associated with stricturing Crohn’s disease, the more aggressive, fibrous form of the disease in which the intestine scars and narrows.

Nearly 75% of patients with low SLC26A6 expression had stricturing disease, raising the possibility that oxalate transporter expression could serve as a molecular signal predicting clinical trajectory—a precision medicine opportunity that warrants validation in larger cohorts.

“Salvador really conceptualized and drove this work from the beginning,” Sheikh said. “She asked a question that hadn’t been asked before: What if a specific dietary molecule is an active driver of gut inflammation in IBD, not just a bystander? The rigor she brought to answering it is what makes these findings so compelling.”

Why it matters for patients

The findings do not call for eliminating plant foods from the IBD diet. Rather, they suggest that for genetically susceptible individuals, even moderate oxalate intake may promote mucosal inflammation and that prior dietary studies in IBD may have been confounded by unmeasured differences in oxalate exposure or handling. Importantly, it is possible to maintain a nutritionally complete, plant-based dietary pattern while reducing total oxalate intake.

The authors also point to the gut microbiome as a promising therapeutic target. Oxalate-degrading bacteria such as Oxalobacter formigenes are depleted in IBD patients, and microbiome-based strategies to optimize oxalate degradation may offer a more sustainable path than dietary restriction alone.

Before formal clinical recommendations regarding dietary oxalate intake, future research should focus on validation in larger, longitudinal patient cohorts that integrate stool oxalate measurements, rigorously captured dietary intake, molecular profiling and microbiome analyses.

“For patients living with Crohn’s disease or ulcerative colitis, this research opens a genuinely new therapeutic angle—one that connects the food on their plate to the inflammation in their gut,” Sheikh said. “Diet is one of the most powerful, modifiable levers we have in medicine, and this study gives us a molecular framework to start using it more precisely.”

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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