Simple Stool Test Flags Hidden Gut Inflammation in Eye Disease Patients

A simple stool test, repeated over time, may reveal hidden gut inflammation in patients whose only symptom is an inflamed eye, according to a prospective cohort study from a Spanish hospital network. Researchers at Gregorio Marañón University General Hospital in Madrid tracked 69 patients with idiopathic uveitis or scleritis—inflammatory eye conditions with no identified cause—and found that a persistently elevated fecal calprotectin trajectory identified a small subgroup harboring subclinical ileitis, an inflammation of the final segment of the small intestine that produces no digestive symptoms. Idiopathic uveitis accounts for an estimated 27 to 51 percent of uveitis cases in Europe and the United States, making it a common and often frustrating diagnostic puzzle.

Because the eye and the gut share immunopathogenic mechanisms, undiagnosed inflammatory bowel disease can lurk behind apparently isolated eye inflammation. Yet subclinical ileitis in this population had never been systematically explored before, the authors note, and identifying it early could allow treatment within what they describe as the inflammatory window of opportunity. The study, published in Frontiers in Medicine, used a serial testing design.

Every participant received a baseline fecal calprotectin measurement, a biomarker of intestinal inflammation. If the result was negative, the test was repeated at six to twelve months; if positive, it was repeated at three months. This allowed the team to define four longitudinal patterns of calprotectin behavior over time, labeled A through D, rather than relying on a single snapshot.

Of the 62 patients with an evaluable outcome, five—8.1 percent—had subclinical ileitis confirmed by capsule endoscopy and/or colonoscopy. The serial approach proved more informative than any single measurement. Baseline fecal calprotectin was significantly higher in patients with confirmed ileitis, with a p-value of 0.024, but the difference became more pronounced at the second determination, where the p-value dropped to 0.002.

The strongest diagnostic balance came from the pattern of persistent elevation, subgroup D. In this group, sensitivity reached 100 percent (exact 95 percent confidence interval 47.8 to 100.0), specificity was 82.5 percent (95 percent CI 70.1 to 91.3), the negative predictive value was 100 percent (95 percent CI 92.5 to 100.0), and the positive likelihood ratio was 5.7 (95 percent CI 3.25 to 10.01). Receiver operating characteristic analysis told a similar story about timing. The second calprotectin determination showed a numerically higher discriminative capacity, with an area under the curve of 0.932 (95 percent CI 0.850 to 1.000), compared with 0.809 (95 percent CI 0.652 to 0.966) for the baseline measurement.

However, a formal DeLong comparison of the two c-statistics found no statistically significant difference between them, with a p-value of 0.242—a reminder that the apparent improvement may reflect the small number of events rather than a true gain in performance. The authors are careful about the limits of their findings. Because subgroups A and C were not endoscopically verified, the reported sensitivity and negative predictive value are estimates conditioned on this particular verification scheme and on only five confirmed events.

They explicitly caution that the results should not be read as validated evidence that a negative calprotectin trajectory excludes subclinical ileitis. The study is described as exploratory and hypothesis-generating, and the team states that confirmation in larger, prospectively verified, multicenter cohorts is required before any screening recommendation can be made. Even so, the study opens an intriguing window onto the gut-eye axis, the emerging concept that intestinal immune activity and ocular inflammation are physiologically entangled.

For now, the message for clinicians is measured rather than prescriptive: among patients with idiopathic uveitis or scleritis, a calprotectin level that stays elevated across repeated measurements identifies a subgroup that may warrant digestive evaluation. With only five confirmed cases and a single-center design, the Madrid team’s findings are best understood as a promising signal—one that larger multicenter studies will need to verify before serial stool testing becomes standard practice in ophthalmology clinics.

Subject of Research: Serial fecal calprotectin screening for subclinical ileitis in patients with idiopathic uveitis or scleritis

Article Title: Serial fecal calprotectin as a screening tool for subclinical ileitis in patients with idiopathic uveitis or scleritis: a prospective cohort study

Article References: Lavilla Olleros, C., Menchén, L., Ramos-Ferreira, J., Merino Rodríguez, B., de Miguel-Yanes, J. M., Gutierrez Bonet, R., Torresano Rodríguez, J., Ausín García, C., Puertas López, C., Alvarez-Sala Walther, L., & Ibares-Frías, L. (2026). Serial fecal calprotectin as a screening tool for subclinical ileitis in patients with idiopathic uveitis or scleritis: a prospective cohort study. Frontiers in Medicine, 13, Article 1968285. https://doi.org/10.3389/fmed.2026.1968285

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1968285

Keywords: fecal calprotectin, uveitis, scleritis, subclinical ileitis, inflammatory bowel disease, gut-eye axis, capsule endoscopy, biomarker, screening, prospective cohort study, ophthalmology, gastroenterology