Zhan Shukai, Liu Caiguang, Meng Jixin, Mao Ren, Tu Tong, Lin Jianming, Chen Minhu, Zeng Zhirong, Zhuang Xiaojun
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Microorganisms. 2023 Mar 20;11(3):794. doi: 10.3390/microorganisms11030794.
Intestinal stricture remains one of the most intractable complications in Crohn's disease (CD), and the involved mechanisms are poorly understood. Accumulating evidence suggests that the gut microbiota contributes to the pathogenesis of intestinal fibrosis. In this study, we investigated specific mucosa-associated microbiota related to intestinal strictures and their role in predicting postoperative disease course. Twenty CD patients who had undergone operative treatments were enrolled and followed up. Intestinal mucosa and full-thickness sections from stenotic and non-stenotic sites were sterilely collected. DNA extraction and bacterial 16s rRNA gene sequencing were conducted. Radiological and histological evaluations were performed to assess fibrosis. Microbial alpha diversity was significantly decreased in stenotic sites ( = 0.009). At the genus level, , , , , and were decreased in stenotic segments ( < 0.1). The difference in sp. (stenotic vs. non-stenotic) was negatively correlated with the erythrocyte sedimentation rate (correlation coefficient (CC) -0.432, = 0.057) and white blood cell count (CC -0.392, = 0.087) and positively correlated with serum free fatty acids (CC 0.575, < 0.05). This difference was negatively associated with intestinal fibrosis evaluated by imagological and histological methods (CC -0.511 and -0.653, < 0.05). Furthermore, CD patients with a higher abundance of sp. in the residual intestine might experience longer remission periods ( < 0.05). The mucosa-associated microbiota varied between stenotic and non-stenotic sites in CD. Most notably, sp. was negatively correlated with intestinal fibrosis and postoperative disease course. It could be a promising biomarker to predict post-operative disease recurrence and a microbial-based therapeutic target.
肠道狭窄仍然是克罗恩病(CD)最棘手的并发症之一,其相关机制尚不清楚。越来越多的证据表明,肠道微生物群与肠道纤维化的发病机制有关。在本研究中,我们调查了与肠道狭窄相关的特定黏膜相关微生物群及其在预测术后疾病进程中的作用。纳入20例接受手术治疗的CD患者并进行随访。无菌采集狭窄部位和非狭窄部位的肠黏膜及全层切片。进行DNA提取和细菌16s rRNA基因测序。进行影像学和组织学评估以评估纤维化。狭窄部位的微生物α多样性显著降低(P = 0.009)。在属水平上,狭窄节段中[具体菌属名称1]、[具体菌属名称2]、[具体菌属名称3]、[具体菌属名称4]、[具体菌属名称5]和[具体菌属名称6]减少(P < 0.1)。[具体菌属名称7]菌(狭窄部位与非狭窄部位相比)的差异与红细胞沉降率呈负相关(相关系数(CC)-0.432,P = 0.057)和白细胞计数呈负相关(CC -0.392,P = 0.087),与血清游离脂肪酸呈正相关(CC 0.575,P < 0.05)。这种差异与通过影像学和组织学方法评估的肠道纤维化呈负相关(CC -0.511和-0.653,P < 0.05)。此外,残留肠道中[具体菌属名称7]菌丰度较高的CD患者可能经历更长的缓解期(P < 0.05)。CD患者狭窄部位和非狭窄部位的黏膜相关微生物群不同。最值得注意的是,[具体菌属名称7]菌与肠道纤维化和术后疾病进程呈负相关。它可能是预测术后疾病复发的有前景的生物标志物和基于微生物的治疗靶点。