Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.
Adipose Tissue
/ microbiology
Animals
Bacterial Translocation
Biodiversity
Biomarkers
/ metabolism
Cell Polarity
Cells, Cultured
Colitis, Ulcerative
/ pathology
Crohn Disease
/ microbiology
Gastrointestinal Microbiome
/ genetics
Gene Expression Regulation
Germ-Free Life
Humans
Ileum
/ microbiology
Lipopolysaccharides
/ metabolism
Macrophages
/ metabolism
Mesentery
/ microbiology
Metagenome
Metagenomics
Mice
Mice, Inbred C57BL
Phenotype
RNA, Ribosomal, 16S
/ genetics
Stem Cells
/ metabolism
Crohn’s disease
adipogenesis
creeping fat
fibrosis
human microbiome
ileum
inflammatory bowel diseases
macrophages
mesenteric adipose
translocation
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
29 10 2020
29 10 2020
Historique:
received:
02
10
2019
revised:
19
07
2020
accepted:
01
09
2020
pubmed:
30
9
2020
medline:
20
5
2021
entrez:
29
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32991841
pii: S0092-8674(20)31150-8
doi: 10.1016/j.cell.2020.09.009
pmc: PMC7521382
pii:
doi:
Substances chimiques
Biomarkers
0
Lipopolysaccharides
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
666-683.e17Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK042086
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062413
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123446
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA243480
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK046763
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests S.D. and C.W.Y.H. are inventors on US patent application #62/679,624.
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