Microbiota in mesenteric adipose tissue from Crohn’s disease promote colitis in mice
Zhen He,
Jinjie Wu,
Junli Gong,
Jia Ke,
Tao Ding,
Wenjing Zhao,
Wai Ming Cheng,
Zhanhao Luo,
Qilang He,
Wanyi Zeng,
Jing Yu,
Na Jiao,
Yanmin Liu,
Bin Zheng,
Lei Dai,
Min Zhi,
Xiaojian Wu,
Christian Jobin,
Ping Lan
Affiliations
Zhen He
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Jinjie Wu
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Junli Gong
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Jia Ke
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Tao Ding
Zhongshan School of Medicine, Sun Yat-sen University
Wenjing Zhao
School of Medicine, Sun Yat-sen University
Wai Ming Cheng
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology
Zhanhao Luo
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology
Qilang He
School of Medicine, Sun Yat-sen University
Wanyi Zeng
School of Medicine, Sun Yat-sen University
Jing Yu
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Na Jiao
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology
Yanmin Liu
Zhongshan School of Medicine, Sun Yat-sen University
Bin Zheng
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Lei Dai
CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences
Min Zhi
Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University
Xiaojian Wu
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Christian Jobin
Department of Medicine, Division of Gastroenterology, University of Florida
Ping Lan
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University
Abstract Background 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. Methods 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. Results 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. Conclusions This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation. Video abstract