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Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans

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Dataset overview

Participants None
Samples None
Reuse readiness 5.9/10 evidence-backed score

Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.

Ha CWY, Martin A, Sepich-Poore GD, Shi B, Wang Y, Gouin K, Humphrey G, Sanders K, et al. · Cell · 2020

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.

doi:10.1016/j.cell.2020.09.009 ↗ PMID 32991841 ↗ PMC7521382 ↗

Study facts

Organism
Homo sapiens
Platform
10x Genomics Chromium and Bio-Rad SureCell
Age group
adult
Disease groups
Non-IBD controls, Ulcerative colitis
Anatomical sites
—

Data availability

  • Analysis code

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Analysis code is available

Limitations

  • Not documented: feature/otu tables are advertised
  • Not documented: taxonomic tables are advertised
  • Not documented: participant counts are documented
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.platform 10x Genomics Chromium and Bio-Rad SureCell
SureCell samples: healthy and inflamed tissue from 3 Crohn's disease patients, 2 ulcerative colitis patients Chromium samples: 2 Crohn's disease patients, 2 non-IBD controls.

Section study.description, offset 5580

Cohort

FieldValueEvidence
cohort.age_group adult
Exclusion criteria included patients under 18, unwilling to provide informed consent, antibiotic or antifungal use in the six weeks prior to surgery, or individuals with colorectal cancer or undergoing chemoradiation therapy.

Section Human subjects, offset —
cohort.non_ibd_controls 2
Chromium samples: 2 Crohn's disease patients, 2 non-IBD controls.

Section study.description, offset 5620
cohort.study_design cross_sectional inferred
patients undergoing surgical resections due to complications from CD

Section Results: Metagenomic Sequencing Reveals Bacterial Translocation, offset 6200
cohort.ulcerative_colitis_participants 2
SureCell samples: healthy and inflamed tissue from 3 Crohn's disease patients, 2 ulcerative colitis patients

Section study.description, offset 5500

Data_Assets

FieldValueEvidence
data_assets.analysis_code True
scRNA-seq codes are available on Github

Section Data availability, offset 117300
data_assets.open_access True from source
"isOpenAccess": "Y"

Section publication metadata, offset —
data_assets.pipeline_or_tool_versions True
Cell Ranger v3.1.0

Section Key Resources Table, offset 80000
data_assets.raw_reads True
All of the DNA and RNA sequencing datasets generated in this study have been deposited to NCBI.

Section Data availability, offset 117000

Specimens

FieldValueEvidence
specimens.body_site mesenteric adipose tissue
Whole blood, resected intestinal tissue, and attached mesenteric adipose were aseptically collected

Section Tissue Collection, offset 100000
specimens.inflamed_status_available True
healthy and inflamed tissue from 3 Crohn's disease patients, 2 ulcerative colitis patients

Section study.description, offset 5500