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克罗恩病术后早期内镜复发的特点是微生物群的明显再定植。

Early Postoperative Endoscopic Recurrence in Crohn's Disease Is Characterised by Distinct Microbiota Recolonisation.

机构信息

Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, Belgium.

Department of Gastroenterology, Vall d'Hebron Research Institute, Barcelona, Spain.

出版信息

J Crohns Colitis. 2020 Nov 7;14(11):1535-1546. doi: 10.1093/ecco-jcc/jjaa081.

DOI:10.1093/ecco-jcc/jjaa081
PMID:32333762
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7648170/
Abstract

BACKGROUND AND AIMS

Intestinal microbiota dysbiosis is implicated in Crohn's disease [CD] and may play an important role in triggering postoperative disease recurrence [POR]. We prospectively studied faecal and mucosal microbial recolonisation following ileocaecal resection to identify the predictive value of recurrence-related microbiota.

METHODS

Mucosal and/or faecal samples from 121 CD patients undergoing ileocaecal resection were collected at predefined time points before and after surgery. Ileal biopsies were collected from 39 healthy controls. POR was defined by a Rutgeerts score ≥i2b. The microbiota was evaluated by 16S rRNA sequencing. Prediction analysis was performed using C5.0 and Random Forest algorithms.

RESULTS

The mucosa-associated microbiota in CD patients was characterised by a depletion of butyrate-producing species (false discovery rate [FDR] <0.01) and enrichment of Proteobacteria [FDR = 0.009] and Akkermansia spp. [FDR = 0.02]. Following resection, a mucosal enrichment of Lachnospiraceae [FDR <0.001] was seen in all patients but in POR patients, also Fusobacteriaceae [FDR <0.001] increased compared with baseline. Patients without POR showed a decrease of Streptococcaceae [FDR = 0.003] and Actinomycineae [FDR = 0.06]. The mucosa-associated microbiota profile had good discriminative power to predict POR, and was superior to clinical risk factors. At Month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes [FDR = 0.04] and Fusobacteria [FDR = 0.04] compared with patients without POR.

CONCLUSIONS

Microbiota recolonisation after ileocaecal resection is different between recurrence and non-recurrence patients, with Fusobacteria as the most prominent player driving early POR. These bacteria involved in the early recolonisation and POR represent a promising therapeutic strategy in the prevention of disease recurrence.

摘要

背景与目的

肠道微生物失调与克罗恩病(CD)有关,可能在触发术后疾病复发(POR)中发挥重要作用。我们前瞻性研究了回肠结肠切除术后粪便和黏膜微生物再定植,以确定与复发相关的微生物的预测价值。

方法

收集 121 例接受回肠结肠切除术的 CD 患者术前和术后规定时间的黏膜和/或粪便样本。从 39 例健康对照中收集回肠活检。POR 通过 Rutgeerts 评分≥i2b 定义。通过 16S rRNA 测序评估微生物群。使用 C5.0 和随机森林算法进行预测分析。

结果

CD 患者的黏膜相关微生物群特征是丁酸产生物种减少(假发现率[FDR]<0.01)和变形菌门富集(FDR=0.009)和 Akkermansia 属富集(FDR=0.02)。切除后,所有患者的黏膜均出现 Lachnospiraceae 富集(FDR<0.001),但 POR 患者与基线相比,还增加了梭杆菌科(FDR<0.001)。无 POR 患者的链球菌科(FDR=0.003)和放线菌科(FDR=0.06)减少。黏膜相关微生物群谱具有良好的鉴别力来预测 POR,并优于临床危险因素。在第 6 个月,经历 POR 的患者的 Negativicutes 科(FDR=0.04)和梭杆菌科(FDR=0.04)的丰度高于无 POR 的患者。

结论

回肠结肠切除术后微生物再定植在复发和非复发患者之间存在差异,梭杆菌是驱动早期 POR 的最突出因素。这些参与早期定植和 POR 的细菌代表了预防疾病复发的有前途的治疗策略。

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