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Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.
Ha, Connie W Y; Martin, Anthony; Sepich-Poore, Gregory D; Shi, Baochen; Wang, Yizhou; Gouin, Kenneth; Humphrey, Gregory; Sanders, Karenina; Ratnayake, Yasiru; Chan, Kelvin S L; Hendrick, Gustaf; Caldera, J R; Arias, Christian; Moskowitz, Jacob E; Ho Sui, Shannan J; Yang, Shaohong; Underhill, David; Brady, Matthew J; Knott, Simon; Kaihara, Kelly; Steinbaugh, Michael J; Li, Huiying; McGovern, Dermot P B; Knight, Rob; Fleshner, Phillip; Devkota, Suzanne.
Affiliation
  • Ha CWY; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Martin A; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Sepich-Poore GD; Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
  • Shi B; Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Wang Y; Applied Genomics, Computation and Translational Core, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Gouin K; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Applied Genomics, Computation and Translational Core, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Humphrey G; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Sanders K; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Ratnayake Y; Trabeya Pte. Ltd., Singapore 018989, Singapore.
  • Chan KSL; Trabeya Pte. Ltd., Singapore 018989, Singapore.
  • Hendrick G; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Caldera JR; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Arias C; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Moskowitz JE; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Ho Sui SJ; Harvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • Yang S; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Underhill D; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Brady MJ; Department of Medicine, Section of Endocrinology and Metabolism, The University of Chicago, Chicago, IL 60637, USA.
  • Knott S; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Applied Genomics, Computation and Translational Core, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Kaihara K; Bio-Rad Genomics, Hercules, CA 94547, USA.
  • Steinbaugh MJ; Harvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • Li H; Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • McGovern DPB; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Knight R; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
  • Fleshner P; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Colorectal Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Devkota S; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: suzanne.devkota@cshs.org.
Cell ; 183(3): 666-683.e17, 2020 10 29.
Article in En | MEDLINE | ID: mdl-32991841
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Adipose Tissue / Bacterial Translocation / Gastrointestinal Microbiome / Mesentery Limits: Animals / Humans Language: En Journal: Cell Year: 2020 Document type: Article Affiliation country: Estados Unidos
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Adipose Tissue / Bacterial Translocation / Gastrointestinal Microbiome / Mesentery Limits: Animals / Humans Language: En Journal: Cell Year: 2020 Document type: Article Affiliation country: Estados Unidos