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肠道微生物群在克罗恩病发病机制中的作用:来自小鼠模型粪便微生物群移植的启示。

Role of gut microbiota in Crohn's disease pathogenesis: Insights from fecal microbiota transplantation in mouse model.

机构信息

Geriatric Surgery of Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.

出版信息

World J Gastroenterol. 2024 Aug 21;30(31):3689-3704. doi: 10.3748/wjg.v30.i31.3689.

DOI:10.3748/wjg.v30.i31.3689
PMID:39193000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11346162/
Abstract

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.

AIM

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.

CONCLUSION

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.

摘要

背景

炎症性肠病,特别是克罗恩病(CD),与肠系膜脂肪组织(MAT)的改变和所谓的“爬行脂肪”现象有关。组织病理学评估显示,CD 患者的 MAT 和肠组织发生了明显改变,这些组织表现为炎症和纤维化。

目的

评估 CD 中 MAT、爬行脂肪、炎症和肠道微生物群之间的复杂相互作用。

方法

从 12 例 CD 患者中收集肠组织和 MAT。分析组织学表现和蛋白表达水平,以确定病变特征。从 5 例最近接受 CD 治疗的患者和 5 例对照中收集粪便样本,并移植到小鼠中。评估和比较移植 CD 患者和对照粪便样本的小鼠的肠道和肠系膜病变以及全身炎症状态。

结果

MAT 的病理学检查显示 CD 受累和未受累结肠之间存在显著差异,包括肠道微生物群结构的显著差异。来自临床健康供体的胎粪微生物群移植(FMT)可改善 2,4,6-三硝基苯磺酸(TNBS)诱导的 CD 小鼠的 CD 症状,而来自 CD 患者的 FMT 则加重了 CD 症状。值得注意的是,FMT 影响了肠道通透性、屏障功能以及促炎因子和脂肪因子的水平。此外,FMT 从 CD 患者加重了 TNBS 诱导的 CD 小鼠结肠组织中的纤维化变化。

结论

肠道微生物群在 CD 的组织病理学中起关键作用。因此,靶向 MAT 和爬行脂肪可能对 CD 患者的治疗具有潜在价值。

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