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粪便微生物移植联合抗生素治疗溃疡性结肠炎后肠道微生物群的变化

Changes in Intestinal Microbiota Following Combination Therapy with Fecal Microbial Transplantation and Antibiotics for Ulcerative Colitis.

作者信息

Ishikawa Dai, Sasaki Takashi, Osada Taro, Kuwahara-Arai Kyoko, Haga Keiichi, Shibuya Tomoyoshi, Hiramatsu Keiichi, Watanabe Sumio

机构信息

Departments of *Gastroenterology, and †Bacteriology, School of Medicine, Juntendo University, Tokyo, Japan.

出版信息

Inflamm Bowel Dis. 2017 Jan;23(1):116-125. doi: 10.1097/MIB.0000000000000975.

DOI:10.1097/MIB.0000000000000975
PMID:27893543
Abstract

BACKGROUND

Fecal microbiota transplantation (FMT) is a potential therapeutic approach to restore normal intestinal microbiota in patients with ulcerative colitis (UC), which is associated with dysbiosis; however, treatment efficacy remains unclear. Hence, we studied the impact of antibiotic pretreatment with amoxicillin, fosfomycin, and metronidazole (AFM therapy) and FMT versus AFM alone.

METHODS

AFM therapy was administered to patients for 2 weeks until 2 days before FMT. Patients' spouses or relatives were selected as donor candidates. Donor fecal samples were collected on the day of administration and transferred into the patient's colon by colonoscopy within 6 hours. Microbiome analysis was performed by 16S rRNA next-generation sequencing.

RESULTS

Patients with mild-to-severe active UC (combination-therapy group, n = 21; AFM monotherapy group, n = 20) were included. Thirty-six patients completed this assessment (combination-therapy group, n = 17; AFM monotherapy group, n = 19). A higher clinical response was observed after combination therapy compared with AFM monotherapy at 4 weeks after treatment. After the 2-week AFM therapy, the Bacteroidetes composition was nearly abolished. The Bacteroidetes proportion recovered in clinical responders at 4 weeks after FMT was not observed in the AFM monotherapy group. Persistent antimicrobial-associated dysbiosis found in the AFM monotherapy group was reversed by FMT. The recovery rate of Bacteroidetes at 4 weeks after FMT correlated with endoscopic severity.

CONCLUSIONS

FMT following antimicrobial bowel cleansing synergistically contributes to the recovery of the Bacteroidetes composition, which is associated with clinical response and UC severity. Thus, this therapeutic protocol may be useful for managing UC.

摘要

背景

粪便微生物群移植(FMT)是一种恢复溃疡性结肠炎(UC)患者正常肠道微生物群的潜在治疗方法,UC与微生物群失调有关;然而,治疗效果仍不明确。因此,我们研究了阿莫西林、磷霉素和甲硝唑联合抗生素预处理(AFM疗法)以及FMT与单独使用AFM的效果对比。

方法

对患者进行2周的AFM疗法,直至FMT前2天。选择患者的配偶或亲属作为供体候选人。在给药当天采集供体粪便样本,并在6小时内通过结肠镜检查将其转移到患者结肠。通过16S rRNA下一代测序进行微生物组分析。

结果

纳入轻度至重度活动性UC患者(联合治疗组,n = 21;AFM单药治疗组,n = 20)。36名患者完成了该评估(联合治疗组,n = 17;AFM单药治疗组,n = 19)。治疗后4周,联合治疗组的临床反应高于AFM单药治疗组。经过2周的AFM治疗后,拟杆菌属的组成几乎消失。AFM单药治疗组未观察到FMT后4周临床缓解者中拟杆菌属比例的恢复。FMT逆转了AFM单药治疗组中持续存在的抗菌药物相关的菌群失调。FMT后4周拟杆菌属的恢复率与内镜严重程度相关。

结论

抗菌肠道清洁后进行FMT协同促进了拟杆菌属组成的恢复,这与临床反应和UC严重程度相关。因此,该治疗方案可能对UC的管理有用。

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