BACKGROUND AND OBJECTIVE: Intestinal mucosal healing is a key indicator for evaluating therapeutic efficacy and predicting long-term prognosis in ulcerative colitis (UC). Short-chain fatty acids (SCFAs) play an important role in maintaining intestinal homeostasis and promoting mucosal repair; however, their quantitative association with UC mucosal healing has not been fully elucidated. This study aimed to investigate the association between SCFA levels and endoscopic mucosal healing in UC patients and evaluate their clinical value as predictive biomarkers. METHODS: This prospective cohort study enrolled 154 UC patients from January 2024 to March 2025, who were divided into a mucosal healing group (n = 68) and a non-healing group (n = 86) according to Mayo endoscopic scores, with an additional 50 healthy controls. Endoscopic evaluations were independently scored by two experienced gastroenterologists with substantial inter-rater reliability (κ = 0.82). Gas chromatography-mass spectrometry was used to detect fecal SCFA concentrations, and real-time quantitative PCR (PCR stands for Polymerase Chain Reaction, a core molecular biology technique that allows for the rapid and specific amplification of specific DNA or RNA fragments in vitro) was employed to detect the expression levels of SCFA transporter protein SLC16A1 and metabolic enzyme genes in mucosal tissues. The association between SCFA levels and mucosal healing indicators was analyzed using multiple logistic regression adjusted for age, gender, disease duration, disease extent, and current medications. RESULTS: The total fecal SCFA concentration in UC patients was significantly lower than that in healthy controls (P < .001). The butyrate concentration in the mucosal healing group was significantly higher than that in the non-healing group (16.8 ± 7.3 vs 10.2 ± 4.6 mmol/kg, P < .001). The SLC16A1 mRNA expression level in the mucosal healing group was 2.3-fold higher than that in the non-healing group, while ACSM3 and ACADS expression levels were elevated by 1.8-fold and 1.6-fold, respectively (all P < .001). Fecal butyrate concentration showed a significant negative correlation with Mayo endoscopic score (r = -0.647, P < .001). Multiple regression analysis revealed that fecal butyrate concentration was an independent predictor of mucosal healing (OR = 1.18, 95% CI: 1.09-1.28, P < .001). Receiver operating characteristic analysis demonstrated that butyrate had an area under the curve (AUC) of 0.847 for predicting mucosal healing, with a sensitivity of 76.5% and specificity of 81.4%. A combined model incorporating butyrate, C-reactive protein, and corticosteroid use achieved superior diagnostic performance (AUC = 0.896). The associations remained consistent across different disease extents and medication subgroups. CONCLUSIONS: Fecal SCFA levels in UC patients, particularly butyrate concentration, are closely associated with the degree of intestinal mucosal healing. Fecal butyrate concentration can serve as a non-invasive biomarker for assessing mucosal healing status in UC patients, providing objective evidence for individualized therapeutic strategy development.
He et al. (Tue,) studied this question.