Background Predictive markers for the outcomes of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) are poorly defined. Existing microbial analyses of FMT efficacy are based on time-consuming and costly sequencing methods, thereby limiting their practical application in clinical settings.

Therefore, we focused on four common siderophores found in Gram-negative pathogens. By analyzing the changes in the total copy number of siderophore genes before and after FMT, we aimed to explore their association with FMT efficacy and evaluate their potential as non-invasive biomarkers for predicting FMT responsiveness.

Methods We enrolled patients with active UC (Mayo score ≥ 3) who underwent two FMT procedures. Fecal samples were collected before and 8 weeks after each FMT session and determined the total copy number of eight siderophore genes, including enterobactin (entF, fepA), salmochelin (iroB, iroN), aerobactin (iucA, iutA), and yersiniabactin (irp1, fyuA). Patients were classified into responder and non-responder groups based on their Mayo scores. The relationship between the total siderophore genes copy number and FMT efficacy was examined.

Results Seventy-two patients with UC underwent FMT. The UC clinical response and remission rates were 62.5% and 19.4% after the first FMT, which increased to 71.7% and 43.4%, respectively, after the second FMT. Compared with the baseline, the total siderophore genes copy number significantly decreased in the responder group, from 1557.32 copies/ng to 251.90 copies/ng after the second FMT. In the non-responder group, the total copy number of siderophore genes showed an increasing trend after the second FMT, from 65.46 copies/ng to 330.78 copies/ng. The total baseline copy number was significantly higher in responders than in non-responders (P < 0.01). A baseline total copy number cutoff value of 289.63 copies/ng showed 85.5% sensitivity and 88.2% specificity in predicting FMT responsiveness.

Conclusions The total copy number of fecal siderophore genes in patients with UC correlates with FMT treatment response, providing a promising biomarker for predicting FMT responsiveness.