A Compound in Spinach and Almonds May Worsen IBD — Because Patients Cannot Clear It

A natural compound found in spinach, almonds and sweet potatoes may aggravate gut inflammation in people with inflammatory bowel disease — not because they eat more of it, but because their intestines handle it differently.

Researchers at the University of North Carolina at Chapel Hill School of Medicine, with Texas A&M and Duke, report that IBD patients have reduced levels of the transporter proteins that remove oxalate from the gut. Published August 13, 2026 in Cellular and Molecular Gastroenterology and Hepatology.

The observation that started it

“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,” said lead researcher Anna Salvador, PhD, RD, LDN.

That dissociation is the whole finding. If intake is equal and output differs, the difference is in handling rather than in diet — which redirects the question from what patients eat to what their intestines do with it.

Establishing equal intake took work. The team combined a Diet History Questionnaire III with DNA metabarcoding of stool, which detects plant material molecularly rather than relying on what participants remember eating — a meaningful improvement, since dietary recall is notoriously unreliable and people with a symptomatic gut condition have particular reason to misreport.

What oxalate is

Oxalate occurs in all plant foods, in widely varying amounts. It is best known outside gastroenterology as the main constituent of most kidney stones, which form when it binds calcium and precipitates.

The body produces some itself and absorbs the rest from food, and it is not metabolised — it must be excreted, either through the kidneys or across the intestinal wall into the gut.

That second route is what this study concerns. The intestine actively secretes oxalate using dedicated transporter proteins, and when that mechanism underperforms, oxalate accumulates where it should have been cleared.

The transporters

The team found lower levels of SLC26A2 and SLC26A3 in intestinal tissue from IBD patients. A related transporter, SLC26A6, produced the sharper clinical association: nearly 75% of patients with low SLC26A6 expression had stricturing Crohn’s disease.

Stricturing disease is the form in which chronic inflammation drives scarring that narrows the bowel, and it is a leading reason Crohn’s patients require surgery. It is also the form that responds least well to drugs controlling inflammation, because fibrosis once established does not reverse when inflammation is suppressed.

An association with that specific phenotype is therefore more interesting than an association with IBD generally.

What the mouse and cell work adds

Mice given an oxalate-supplemented diet alongside a colitis-inducing substance were 60% less likely to survive than controls. In genetically susceptible mice, oxalate accelerated disease onset and increased severity.

Crucially, the transporter genes showed reduced activity before dietary intervention — which matters for the direction of causation. If the transporter deficit preceded the oxalate exposure, it is more plausibly a predisposing factor than a consequence of inflammation.

In culture, macrophages and dendritic cells exposed to oxalate mounted intensified inflammatory responses, supplying a cellular mechanism for how accumulated oxalate would amplify rather than merely accompany gut inflammation.

Why this is not dietary advice

The authors are explicit that the findings “are not yet sufficient to support formal recommendations about oxalate intake for people with IBD,” and that the SLC26A6 association needs confirmation in larger patient groups.

The caution is well placed, and the reason is worth stating plainly: the foods highest in oxalate are spinach, nuts, beans, sweet potatoes and whole grains. Advising IBD patients to avoid them would remove much of a plant-rich diet from a population already at risk of nutritional deficiency, based on a mechanism not yet confirmed clinically.

“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,” said lab director Shehzad Z. Sheikh, MD, PhD.

The word doing the work there is precisely. A framework identifying which patients cannot clear oxalate would allow targeted restriction, which is a different proposition from advising everyone with IBD to avoid spinach.

Why diet research in IBD has been so unsatisfying

Patients with inflammatory bowel disease ask what they should eat more consistently than almost any other question, and the evidence base has struggled to answer it.

Part of the difficulty is reverse causation. People with active disease change what they eat to manage symptoms, so any cross-sectional association between a food and disease activity may reflect the disease driving the diet rather than the reverse.

Part is heterogeneity. Crohn’s disease and ulcerative colitis differ, and within Crohn’s the inflammatory, stricturing and penetrating phenotypes behave differently — so a dietary factor mattering to one subgroup is diluted across a mixed cohort.

And elimination diets are close to impossible to blind. A patient knows whether they are avoiding a food, and outcome measures in IBD lean on symptom reporting, which expectation influences.

What distinguishes this work is that it starts from a molecular defect rather than from a food. Identifying which patients carry a transporter deficit offers a way to define the subgroup in advance — which is the missing ingredient that has made dietary trials in IBD so hard to interpret.

Funding came from the Helmsley Charitable Trust, NIDDK, the Chan Zuckerberg Initiative, Schmidt Sciences, the Burroughs Wellcome Fund and additional NIH sources. Research news, not dietary or medical advice.