Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans
| Autor: | Shannan J. Ho Sui, Anthony Martin, Kelly Kaihara, Karenina Sanders, Gregory Humphrey, Jacob E. Moskowitz, J.R. Caldera, Phillip Fleshner, Michael J. Steinbaugh, Matthew J. Brady, Huiying Li, Rob Knight, Yasiru Ratnayake, Connie W.Y. Ha, Kelvin S.L. Chan, Yizhou Wang, Kenneth Gouin, Suzanne Devkota, Dermot P.B. McGovern, David M. Underhill, Baochen Shi, Simon R.V. Knott, Gustaf Hendrick, Shaohong Yang, Christian Arias, Gregory D. Sepich-Poore |
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| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Crohn’s disease Adipose tissue translocation Chromosomal translocation Ulcerative Crohn's Disease Gut flora Inbred C57BL Medical and Health Sciences Oral and gastrointestinal Mice 0302 clinical medicine Crohn Disease Fibrosis RNA Ribosomal 16S 2.1 Biological and endogenous factors Mesentery Aetiology Cells Cultured 0303 health sciences Clostridium innocuum Cultured biology Stem Cells Cell Polarity human microbiome Biodiversity Biological Sciences Colitis macrophages mesenteric adipose medicine.anatomical_structure Phenotype Adipose Tissue Adipogenesis ileum 16S Cells Ileum inflammatory bowel diseases General Biochemistry Genetics and Molecular Biology Article Microbiology adipogenesis 03 medical and health sciences Immune system medicine Animals Humans Germ-Free Life 030304 developmental biology Ribosomal Macrophages Prevention fibrosis Inflammatory Bowel Disease biology.organism_classification medicine.disease Gastrointestinal Microbiome Mice Inbred C57BL Gene Expression Regulation Bacterial Translocation RNA Metagenome Colitis Ulcerative Metagenomics creeping fat Digestive Diseases 030217 neurology & neurosurgery Biomarkers Developmental Biology |
| Zdroj: | Cell, vol 183, iss 3 Cell |
| Popis: | A mysterious feature of Crohn’s disease (CD) is the extra-intestinal manifestation of “creeping fat” (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria. Graphical Abstract Highlights • Gut bacterial translocation to mesenteric adipose tissue (MAT) naturally occurs • MAT from Crohn’s disease (CD) harbors a bacterial consortium defined by C. innocuum • These bacteria in CD promote restructuring of MAT and formation of “creeping fat” • Creeping fat expansion and fibrosis prevent systemic translocation of gut bacteria Ha et al. provide evidence that, in humans with inflammatory bowel disease, the phenomenon known as “creeping fat” is a protective response where mesenteric adipose tissue migrates (or “creeps”) to sites of gut barrier dysfunction to prevent systemic dissemination of potentially harmful bacterial antigens that have translocated across the barrier from the gut lumen. |
| Databáze: | OpenAIRE |
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