背景:活动性溃疡性结肠炎(UC)患者粪便微生物移植(FMT)结局的预测标志物定义不明确。我们旨在研究FMT前后肠道微生物群的变化,并评估确定粪便细菌铁载体基因总拷贝数在预测FMT反应性方面的潜在价值。
方法:纳入接受过两次FMT手术的活动性UC患者(Mayo评分≥3)。在每个FMT疗程之前和之后8周收集粪便样品。患者分为临床反应和无反应组,根据他们的Mayo得分.使用宏基因组测序获取粪便微生物区系谱,通过定量实时聚合酶链反应和总铁载体基因拷贝数。此外,我们研究了铁载体基因总拷贝数与FMT疗效之间的关联.
结果:70例UC患者接受了FMT。首次FMT手术后的临床反应和缓解率分别为50%和10%,第二次FMT后分别提高到72.41%和27.59%。累积临床反应和临床缓解率分别为72.86%和25.71%。与基线相比,反应组显示粪杆菌显著增加,肠杆菌科细菌的减少,与第二次FMT后总细菌铁载体基因拷贝数的变化有关(1889.14vs.98.73拷贝/ng,P<0.01)。毒力因子分析显示富集的铁摄取系统,尤其是细菌铁载体,在FMT前的反应组中,大肠杆菌的贡献更大。应答组的总基线拷贝数显著高于非应答组(1889.14vs.94.86拷贝/ng,P<0.01)。755.88拷贝/ng的总基线拷贝数截断值在预测FMT反应性方面显示出94.7%的特异性和72.5%的灵敏度。
结论:粪杆菌显著增加,FMT后,在应答者中观察到肠杆菌科细菌和总粪便铁载体基因拷贝数的减少。铁载体基因及其编码细菌可能对FMT对活动性溃疡性结肠炎的临床反应具有预测价值。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.