Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China.
Microbiome. 2021 Nov 23;9(1):228. doi: 10.1186/s40168-021-01178-8.
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.
肠系膜脂肪组织（mAT）增生，即“ creeping fat”，是克罗恩病（CD）的一种病理特征。手术中储备的 creeping fat 与 CD 患者的预后不良相关，但具体机制尚不清楚。
采用 CD 患者 48 例和非 CD 对照 16 例的队列，对肠系膜微生物组、代谢组和宿主转录组进行了特征描述。整合多维数据，包括 16S 核糖体 RNA 基因测序（16S rRNA）、宿主 RNA 测序和代谢组学，以揭示网络相互作用。从 mAT 中分离肠系膜常驻细菌，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，以验证其促炎作用。
肠系膜微生物群导致 CD 患者 mAT 中异常代谢产物的产生和转录。mAT 常驻菌群的存在与 CD 的发生有关。从 CD mAT 中分离出的不动杆菌（A. pulmonis）可转移至 mAT，并加重 DSS 诱导的和 Il10 基因缺陷（Il10）自发性结肠炎在小鼠中。CD 患者 mAT 和黏膜层中的 A. pulmonis 水平均高于非 CD 组。
本研究表明，CD 患者的肠系膜微生物群塑造了有害的微环境，并促进了肠道炎症。视频摘要。
