Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn’s disease. Patients with Crohn’s disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn’s disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn’s disease recurrence.

中文翻译：

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手术诱导缓解后，回肠和结肠粘膜相关微生物群预测克罗恩病复发


研究手术诱导缓解后的组织相关微生物群可能有助于了解克罗恩病肠道炎症的引发机制。在 6 个学术中心前瞻性招募了接受回结肠切除术的克罗恩病患者。来自新末端回肠、结肠和直肠乙状结肠的活检样本是通过手术后进行的结肠镜检查获得的。提取微生物DNA用于16S rRNA基因测序。分析了微生物多样性和分类学差异相对丰度。应用随机森林模型来分析临床和微生物特征的表现以预测复发。 Rutgeerts评分≥i2被视为内镜下复发。总共分析了 262 名克罗恩病患者的 349 份术后结肠镜检查和 944 份活检样本。回肠炎症解释了回肠和结肠粘膜相关微生物群的大部分解释差异。与仍处于内镜缓解状态的患者相比，从 97 名在第一次术后结肠镜检查时处于手术诱导缓解但在第二次结肠镜检查时出现内镜复发的患者中获得的样本显示出较低的多样性和微生物偏差。 3 个活检部位的 Gammaproteobacteria 属的减少和几个属的增加会增加进一步复发的风险。肠道微生物组能够比临床特征更好地预测未来的复发。回肠和结肠粘膜相关的微生物组偏差先于手术诱导缓解后新发回肠炎症的发展，并对未来的复发表现出良好的预测性能。 这些发现表明，有针对性的微生物调节是预防术后克罗恩病复发的一种可行方法。