背景:炎症性肠病,特别是克罗恩病(CD),与肠系膜脂肪组织(MAT)的改变和称为“爬行脂肪”的现象有关。组织病理学评价显示,CD患者MAT和肠组织发生显著改变,这些组织的特征是炎症和纤维化。
目的:为了评估MAT,爬行脂肪,炎症,和CD中的肠道微生物群。
方法:收集12例CD患者的肠组织和MAT。分析组织学表现和蛋白质表达水平以确定病变特征。从五名最近治疗的CD患者和五名对照受试者收集粪便样品并移植到小鼠中。这些小鼠的肠道和肠系膜病变,以及他们的全身炎症状态,在移植了CD患者和对照组粪便样本的小鼠中进行评估和比较。
结果:MAT的病理学检查显示,受CD影响的结肠和未受影响的结肠之间存在显着差异,包括肠道菌群结构的显著差异。来自临床健康供体的胎儿微生物群移植(FMT)到2,4,6-三硝基苯磺酸(TNBS)诱导的CD小鼠中,改善了CD症状,而来自CD患者的FMT进入这些小鼠会加剧CD症状。值得注意的是,FMT影响肠道通透性,屏障功能,以及促炎因子和脂肪因子的水平。此外,CD患者的FMT加剧了TNBS诱导的CD小鼠结肠组织的纤维化变化。
结论:肠道菌群在CD的组织病理学中起关键作用。因此,靶向MAT和爬行脂肪可能具有治疗CD患者的潜力。
BACKGROUND: Inflammatory bowel disease, particularly Crohn\'s disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed \"creeping fat\". Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis.
OBJECTIVE: To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD.
METHODS: Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.
RESULTS: Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.
CONCLUSIONS: Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.