患者与供体的相似性以及供体来源的物种会影响溃疡性结肠炎粪便微生物群移植的结果。

Patient-donor similarity and donor-derived species contribute to the outcome of fecal microbiota transplantation for ulcerative colitis.

作者信息

Ishikawa Dai, Watanabe Hikaru, Nomura Kei, Zhang Xiaochen, Maruyama Takafumi, Odakura Rina, Koma Masao, Shibuya Tomoyoshi, Osada Taro, Fukuda Shinji, Nakahara Taku, Terauchi Jun, Nagahara Akihito, Yamada Takuji

机构信息

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

出版信息

J Crohns Colitis. 2025 Apr 4;19(4). doi: 10.1093/ecco-jcc/jjaf054.

DOI:10.1093/ecco-jcc/jjaf054

PMID:40168084

Abstract

BACKGROUND AND AIMS

Clinical applications of fecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonization of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of the administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching.

METHODS

Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 fecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one-patient-to-one-donor strategy.

RESULTS

Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (P = .027), immunosuppressants (P = .049), and biologics (P = .029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; P = .03, LTR; P = .05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (P < .05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric-acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (P < .05).

CONCLUSIONS

This study provides important insights for developing patient-tailored FMT-based therapies for UC.

摘要

背景与目的

粪便微生物群移植（FMT）在治疗溃疡性结肠炎（UC）的临床应用中已显示出有前景的结果。然而，FMT的有益效果是否归因于供体来源的物种在患者体内的转移和定植仍不清楚。在此，我们研究了影响三联抗生素给药FMT（A-FMT）疗效的因素以及合适供体和患者-供体匹配的标准。

方法

2014年3月至2019年10月期间入组的97例活动期UC患者接受了FMT。基于A-FMT后4周Lichtiger临床活动指数的降低评估临床特征，长期缓解者（LTR）定义为A-FMT后12个月内无病情加重的患者。对采用一对一供体策略分配的49例患者-供体组合的147份粪便样本（A-FMT前、A-FMT后和供体）进行微生物组分析。

结果

97例患者中，61例获得临床缓解，其中35例被归类为临床缓解。A-FMT的疗效受UC严重程度以及先前使用类固醇（P = 0.027）、免疫抑制剂（P = 0.049）和生物制剂（P = 0.029）的影响。有效供体富含诸如拟杆菌门等在UC中减少的分类群，与无反应者相比，反应者中“患者来源”和“新扩增子序列变体”分类群的丰度显著较低（缓解；P = 0.03，LTR；P = 0.05）。“供体来源”的扩增子序列变体序列——颤螺菌科UCG-002和alistipes在反应者中显著富集（P < 0.05）。我们的结果表明，患者的分类组成以及患者-供体微生物群中拟杆菌和产丁酸细菌的相似性显著影响A-FMT疗效（P < 0.05）。