Microbiota in mesenteric adipose tissue from Crohn's disease promote colitis in mice.

Microbiota in mesenteric adipose tissue from Crohn's disease promote colitis in mice.
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克罗恩病肠系膜脂肪组织中的微生物群促进小鼠结肠炎

DOI:
10.1186/s40168-021-01178-8
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发表时间:
2021-11-23
期刊:
影响因子:
15.5
通讯作者:
Lan P
Lan P
中科院分区:
生物学1区
文献类型:
--
作者:
He Z;Wu J;Gong J;Ke J;Ding T;Zhao W;Cheng WM;Luo Z;He Q;Zeng W;Yu J;Jiao N;Liu Y;Zheng B;Dai L;Zhi M;Wu X;Jobin C;Lan P

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肠系膜脂肪组织(MAT)增生,称为爬行脂肪,是克罗恩病(CD)的病理特征。手术中的爬行脂肪储备与CD患者预后不良有关,但其机制尚不清楚。对48例CD患者和16例非CD对照的肠系膜微生物组、代谢组和宿主转录组进行了研究。包括16S核糖体RNA基因测序(16S RRNA)、宿主RNA测序和代谢组在内的多维数据被整合以揭示网络相互作用。从MAT中分离出肠系膜驻留细菌,并在葡聚糖硫酸钠(DSS)模型和IL10基因缺陷(IL10−/−)小鼠结肠炎模型中进行功能研究,以验证它们的促炎作用。肠系膜微生物区系有助于CD患者MAT中异常代谢物的产生和转录本的产生。Mat驻留微生物区系的存在与Cd的发育有关。从CD垫上分离到的肺无色杆菌可移位到MAT上,并可加重DSS诱导的小鼠自发性结肠炎和IL10基因缺陷(IL10−/−)小鼠的自发性结肠炎。CD组垫层和粘膜层的肺泡灌洗液中肺泡灌洗液中肺炎支原体水平均高于非CD组。这项研究表明,CD患者的肠系膜微生物区系形成了有害的微环境,促进了肠道炎症。视频摘要在线版本包含补充材料,可在10.1186/s40168021-021-8上查阅。
Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat is a pathologic characteristic of Crohn’s disease (CD). The reserve of creeping fat in surgery is associated with poor prognosis of CD patients, but the mechanism remains unknown. Mesenteric microbiome, metabolome, and host transcriptome were characterized using a cohort of 48 patients with CD and 16 non-CD controls. Multidimensional data including 16S ribosomal RNA gene sequencing (16S rRNA), host RNA sequencing, and metabolome were integrated to reveal network interaction. Mesenteric resident bacteria were isolated from mAT and functionally investigated both in the dextran sulfate sodium (DSS) model and in the Il10 gene-deficient (Il10−/−) mouse colitis model to validate their pro-inflammatory roles. Mesenteric microbiota contributed to aberrant metabolites production and transcripts in mATs from patients with CD. The presence of mAT resident microbiota was associated with the development of CD. Achromobacter pulmonis (A. pulmonis) isolated from CD mAT could translocate to mAT and exacerbate both DSS-induced and Il10 gene-deficient (Il10−/−) spontaneous colitis in mice. The levels of A. pulmonis in both mAT and mucous layer from CD patients were higher compared to those from the non-CD group. This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation. Video abstract The online version contains supplementary material available at 10.1186/s40168-021-01178-8.
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