Oxalates can exacerbate inflammation in diseases of the gastrointestinal tract

We are talking about oxalate — a natural compound found in all plant‑based foods. In a healthy person, most dietary oxalate is excreted through the intestines. However, in patients with ulcerative colitis and Crohn’s disease, this mechanism has been found to be disrupted. Scientists have discovered that the transport proteins SLC26A2 and SLC26A3, which are responsible for the absorption of oxalate from the intestines, are consistently reduced in such patients; the more severe the inflammation, the lower their levels. As a result, oxalate accumulates in the intestinal environment and, as data show, intensifies inflammation.

The paradox that was recorded for the first time is as follows. Patients with Crohn’s disease consumed approximately the same amount of plant‑based food as healthy individuals; this was confirmed by two independent methods: a validated food questionnaire and DNA metabarcoding, a molecular technique that identifies plant species in stool samples. Prior to this, such an approach had not been used to assess diet in patients with inflammatory bowel diseases. Nevertheless, the level of oxalate in the stool of patients with Crohn’s disease was significantly higher. This means that the problem is not so much how much oxalate a person consumes, but how their intestines deal with this compound.

The results in humans were supported by experiments on mice. Rodents that received oxalate together with a substance that causes colitis survived 60 % less often than those who did not receive oxalate supplements. In two independent models of mice with a genetic predisposition to colitis, dietary oxalate accelerated the onset of the disease and exacerbated its severity. Notably, the oxalate transport genes in these mice were reduced even before the supplement was introduced, just like in patients. And in cell culture, oxalate enhanced the inflammatory response of macrophages and dendritic cells, which play an important role in intestinal immunity.

Researchers also found that low levels of another transporter, SLC26A6, are associated with the structural form of Crohn’s disease — that is, a more aggressive variant in which the intestine becomes scarred and narrowed. About 75 % of patients with low SLC26A6 levels had this particular form. This offers hope that the expression of oxalate transporters may become a molecular signal predicting the clinical course of the disease — a possibility that will need to be tested in larger cohorts.

The findings do not mean that plant‑based foods need to be excluded from the diet in cases of inflammatory bowel diseases. The point is that for people with a genetic predisposition, even moderate oxalate intake can exacerbate mucosal inflammation, and it is possible to maintain a balanced plant‑based diet while reducing the overall oxalate content. Another promising avenue is the gut microbiome: bacteria that break down oxalate, such as Oxalobacter formigenes, are depleted in patients with inflammatory diseases, and microbiome‑based strategies may prove more sustainable than dietary restrictions alone.