A compound in spinach and almonds may be quietly worsening Crohn’s and colitis

A new study from the UNC School of Medicine found that oxalate, a compound naturally present in spinach, almonds and sweet potatoes, may worsen gut inflammation in people with Crohn’s disease and ulcerative colitis by exploiting a transport system that malfunctions in their intestines. Led by postdoctoral scholar Anna Salvador in the lab of Shehzad Z. Sheikh, a professor of medicine and genetics at the UNC School of Medicine, the study found that two oxalate transporter proteins, SLC26A2 and SLC26A3, are consistently reduced in gut tissue from both ulcerative colitis and Crohn’s disease patients. The more inflamed the tissue, the lower the transporter levels drop.

Oxalate occurs naturally in all plant foods and is normally eliminated in stool even in a healthy gut. When the transporters that absorb it are impaired, the compound accumulates in the intestinal environment instead, where the study’s data suggest it amplifies the same inflammation that defines inflammatory bowel disease.

DNA Metabarcoding Found a Dietary Paradox in Crohn’s Patients

Crohn’s disease patients had significantly higher stool oxalate levels than people without inflammatory bowel disease, even though both groups reported eating similar amounts of plant-based food. Salvador’s team confirmed that pattern two independent ways: a validated dietary questionnaire and DNA metabarcoding, a molecular technique that identifies which plant species show up in a stool sample, marking the first time metabarcoding has been used to assess diet in an inflammatory bowel disease population. Salvador said the matching intake numbers told the team the difference was not about what patients were eating, but about something fundamentally different in how their gut handles oxalate once it arrives — the biological signal that pointed the study toward the reduced SLC26A2 and SLC26A3 transporter activity at the center of the findings.

Mice Fed Oxalate Alongside Colitis Were 60% Less Likely to Survive

The human findings held up in controlled animal experiments. Mice fed an oxalate-supplemented diet alongside a colitis-inducing agent were 60% less likely to survive than mice not given dietary oxalate, and in two separate, genetically susceptible mouse models of spontaneous colitis, added oxalate accelerated how quickly disease set in and made it worse once it did. Critically, the oxalate transporter genes were already reduced at baseline in those susceptible mice before any oxalate was introduced, mirroring the pattern researchers saw in human patients. In cell culture experiments, oxalate exaggerated inflammatory responses in macrophages and dendritic cells, the immune cells that help set the gut’s inflammatory tone.

A Third Transporter May Predict Which Crohn’s Cases Turn Severe

In an exploratory analysis, low expression of a third transporter, SLC26A6, tracked with a more aggressive form of the disease. Nearly 75% of patients with low SLC26A6 expression had stricturing Crohn’s disease, the fibrous form in which the intestine scars and narrows, raising the possibility that transporter expression could eventually work as a molecular signal for predicting how a patient’s disease will progress. If validated in larger cohorts, SLC26A6 expression could function similarly to genetic markers already used elsewhere in gastroenterology, flagging which newly diagnosed Crohn’s patients are more likely to develop the scarring, narrowing complications that often require surgery, well before those complications show up on a scan. “Dr. 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.”

Researchers Say This Isn’t a Case for Cutting Plant Foods

The findings do not call for eliminating spinach, almonds or other plant foods from the diets of people with inflammatory bowel disease. Instead, the authors say genetically susceptible patients may benefit from moderating total oxalate intake while still eating a nutritionally complete, plant-based diet, and they point to the gut microbiome as a promising treatment angle since oxalate-degrading bacteria such as Oxalobacter formigenes are depleted in inflammatory bowel disease patients. Oxalobacter formigenes specializes in breaking oxalate down before it can accumulate in the gut, which gives researchers a specific microbial target rather than a vague instruction to eat differently — restoring that bacterium, or engineering a probiotic strategy that mimics what it does, is the kind of intervention the authors say could let patients keep eating plant-based diets while lowering the oxalate load their inflamed intestines struggle to handle.

Sheikh said the research, published in Cellular and Molecular Gastroenterology and Hepatology, opens a genuinely new therapeutic angle connecting the food on a patient’s plate to the inflammation in their gut. Before any formal dietary recommendation follows, the team says future research needs larger, longitudinal patient cohorts that combine stool oxalate measurements, carefully tracked diets, molecular profiling and microbiome analysis in one study. The work drew on collaborators across the UNC School of Medicine, Texas A&M University and Duke University, and was supported by the Helmsley Charitable Trust, the National Institute of Diabetes and Digestive and Kidney Diseases, the Chan Zuckerberg Initiative, Schmidt Sciences and the Burroughs Wellcome Fund, funding that let the team run human, mouse and cell culture experiments side by side rather than one at a time.

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This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.