School of Medicine, Nankai University, Tianjin, 300071, China.
Microbiota Laboratory and Microbiota Division, Department of Gastroenterology and Hepatology, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.
J Transl Med. 2024 Jun 24;22(1):589. doi: 10.1186/s12967-024-05419-w.
Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness.
Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy.
Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness.
A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.
粪便微生物群移植（FMT）治疗活动期溃疡性结肠炎（UC）的预测标志物尚未明确。本研究旨在探讨 FMT 治疗前后肠道微生物群的变化，并评估粪便细菌铁载体总拷贝数在预测 FMT 反应中的潜在价值。
本研究纳入了接受了两次 FMT 治疗的活动期 UC 患者（Mayo 评分≥3）。收集了每次 FMT 治疗前后的粪便样本。根据 Mayo 评分，患者被分为临床反应组和非反应组。采用宏基因组测序检测粪便微生物群谱，采用实时定量聚合酶链反应检测粪便铁载体总拷贝数。此外，我们还研究了粪便铁载体总拷贝数与 FMT 疗效之间的关系。
70 例 UC 患者接受了 FMT。第一次 FMT 后，临床反应率和缓解率分别为 50%和 10%，第二次 FMT 后分别增加至 72.41%和 27.59%。累积临床反应率和临床缓解率分别为 72.86%和 25.71%。与基线相比，反应组的粪杆菌显著增加，肠杆菌科减少，第二次 FMT 后总细菌铁载体基因拷贝数也发生了变化（1889.14 对 98.73 拷贝/ng，P<0.01）。毒力因子分析显示，铁摄取系统，尤其是细菌铁载体，在 FMT 前反应组中富集，大肠杆菌的贡献更大。反应组的总基线拷贝数明显高于非反应组（1889.14 对 94.86 拷贝/ng，P<0.01）。总基线拷贝数截断值为 755.88 拷贝/ng 时，预测 FMT 反应性的特异性为 94.7%，敏感性为 72.5%。
FMT 后反应者粪便中粪杆菌显著增加，肠杆菌科和总粪便铁载体基因拷贝数减少。铁载体基因及其编码细菌可能对 FMT 治疗活动期溃疡性结肠炎的临床反应有预测价值。
