IDDF2024-ABS-0323 Fecal siderophore genes are potential biomarker for ulcerative colitis

Background Non-invasive biomarkers are currently recommended for assessing ulcerative colitis (UC) disease activity. Gut microbiome-related biomarkers are used as direct indicators of the intestinal microbiota and have considerable potential for disease assessment and therapeutic guidance in UC. This study aims to explore the relationship between fecal siderophore genes and UC activity and their potential value as a non-invasive biomarker to evaluate UC activity. Methods We included 166 patients with active UC (37 mild, 83 moderate, and 46 severe cases) and 165 healthy controls (HCs). Quantitative real-time PCR were used for the detection of eight siderophore genes, including enterobactin (entF, fepA), salmochelin (iroB, iroN), aerobactin (iucA, iutA), and yersiniabactin (irp1, fyuA). Results Patients with UC showed higher siderophore gene total copy number than HCs (1182.49 vs. 176.44 copies/ng, P<0.01). A threshold of 2877.68 copies/ng distinguished patients with active UC from HCs, with 90.3% specificity and 33.1% sensitivity. Based on clinical disease activity, the total copy number of siderophore genes was significantly higher in patients with severe active UC than in those with moderate (3111.03 vs 1183.54 copies/ng, P<0.05) and mild (3111.03 vs 672.60 copies/ng, P<0.01) active UC. Moreover, patients with severe endoscopic activity exhibited an increased total copy number of fecal siderophore genes, higher than that in patients with mild-to-moderate endoscopic activity (1318.02 vs. 723.10 copies/ng, P<0.05). A threshold of 10 298.63 copies/ng achieved 92.5% specificity and 43.5% sensitivity in identifying severe active UC, and 94% specificity and 22.5% sensitivity in identifying endoscopic severe active UC. In parallel test with serum C-reactive protein, the sensitivity and specificity increased to 89.1% and 75.8% for the clinical severe active stage and 55.2% and 88.0% for the endoscopic severe active stage, respectively. Conclusions Total siderophore gene copy number was positively correlated with both clinical and endoscopic disease activity in UC. The high prevalence and total copy number of bacterial siderophore genes indicated that they potentially serve as a novel non-invasive biomarker for UC activity.