Fecal butyric acid as a predictive biomarker of endoscopic remission in inflammatory bowel disease: a multicenter prospective study

Introduction
Effective prediction of endoscopic remission is a key to optimizing ulcerative colitis (UC) management. While fecal calprotectin (FC) is widely used, its limitations highlight the need for complementary biomarkers. This study evaluated fecal butyric acid (C4) as a novel, non-invasive predictor of endoscopic remission in UC.

Aim
To assess the association between fecal C4 levels and endoscopic remission (Mayo score 0), and secondarily/also, the correlation between C4 and FC.

Material and methods
A multicenter, prospective study enrolled 100 UC patients between April 2021 and April 2023, including 26 in remission and 74 with active disease. Inclusion criteria were confirmed UC diagnosis for ≥ 1 year and stable therapy without medication changes. Fecal C4 was measured using mass spectrometry. Analyses included descriptive statistics, group comparisons, receiver operating characteristic (ROC) curve analysis, and Spearman correlation.

Results
Patients in remission had significantly higher fecal C4 levels (mean difference: 4.05 nM/mg; 95% CI: 2.44–5.71; p < 0.001) and lower Mayo scores. C4 showed excellent predictive performance (area under the curve (AUC) = 0.943; 95% CI: 0.897–0.980; p < 0.001), with 100% sensitivity and 86% specificity at a cutoff of 1.68 nM/mg. No significant correlation was found between C4 and FC.

Conclusions
Fecal C4 is a promising biomarker for predicting endoscopic remission in UC, offering high sensitivity and specificity. Its use may enhance clinical decision-making and support individualized treatment approaches. Further validation in larger cohorts is warranted to confirm these findings and establish its clinical utility.