Foundry120 atlas

← IBD microbiome

Microbial diversity in human creeping fat, mesenteric adipose tissue and underlying intestinal mucosa

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Dataset overview

Participants 28
Samples 131
Reuse readiness 7.6/10 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
—
Platform
Illumina NovaSeq 6000
Age group
adult
Disease groups
Crohn's disease, Non-IBD controls, Ulcerative colitis
Anatomical sites
—

Data availability

Specific data assets have not been resolved from the source yet — see the source repository below for the full file listing.

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Feature/OTU tables are advertised
  • Taxonomic tables are advertised
  • Participant-to-sample mapping is available
  • Participant counts are documented
  • Sample counts are documented
Extraction evidence & provenance

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

Assay

FieldValueEvidence
assay.paired_end True
paired-end 2x150bp sequencing

Section DNA extraction and library preparation for deep shotgun sequencing, offset 108000
assay.platform Illumina NovaSeq 6000
paired-end 2x150bp sequencing using a S4 flow cell of a NovaSeq 6000 instrument

Section DNA extraction and library preparation for deep shotgun sequencing, offset 108000
assay.primers_reported True
bacterial 16S sequencing (V4 region) and fungal ITS sequencing (ITS1 region)

Section DNA extraction for 16S and ITS sequencing, offset 106500
assay.read_length 150
paired-end 2x150bp sequencing

Section DNA extraction and library preparation for deep shotgun sequencing, offset 108000

Cohort

FieldValueEvidence
cohort.age_group adult
Exclusion criteria included patients under 18

Section Human subjects, offset 89500
cohort.crohns_disease_participants 11
obtained from 11 patients undergoing surgical resections due to complications from CD

Section Results—Metagenomic Sequencing Reveals Bacterial Translocation, offset 8500
cohort.non_ibd_controls 4
healthy tissue controls from ileal mucosa (H Muc) and attached MAT (H MAT) and blood from four subjects

Section Results—Metagenomic Sequencing Reveals Bacterial Translocation, offset 8950
cohort.study_design cross_sectional inferred
Surgical resection specimens were collected from healthy ileal controls and patients... undergoing intestinal resection

Section Human subjects, offset 89500
cohort.total_participants 28
obtained from 11 patients undergoing surgical resections due to complications from CD... 13 UC patients... healthy tissue controls... from four subjects

Section Results—Metagenomic Sequencing Reveals Bacterial Translocation, offset 8500
cohort.treatment_exposure_documented True
Patient metadata including clinical characteristics, medication use, family history, social history, and demographic information

Section Results—Metagenomic Sequencing Reveals Bacterial Translocation, offset 9400
cohort.ulcerative_colitis_participants 13
13 UC patients as controls who exhibit intestinal inflammation in the absence of CrF

Section Results—Metagenomic Sequencing Reveals Bacterial Translocation, offset 8750

Data_Assets

FieldValueEvidence
data_assets.feature_or_otu_table True
leaving 2,803 gOTUs available for downstream analyses across all samples

Section Bioinformatic processing of shotgun sequencing samples, offset 114500
data_assets.open_access True from source
isOpenAccess: "Y"

Section Publication metadata, offset —
data_assets.qc_or_negative_controls_reported True
a total of four negative control blanks were processed alongside the samples during library preparation

Section DNA extraction and library preparation for deep shotgun sequencing, offset 108300
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 90000
data_assets.taxonomic_table True
gOTU table generation and functional pathway characterization on a per-sample basis

Section Bioinformatic processing of shotgun sequencing samples, offset 114500

Specimens

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

Section Method Details—Tissue Collection, offset 102000
specimens.inflamed_status_available True
Paired involved and adjacent uninvolved ileal segments

Section Results—Metagenomic Sequencing Reveals Bacterial Translocation, offset 8300
specimens.longitudinal_sampling False inferred
Surgical resection specimens were collected... undergoing intestinal resection

Section Human subjects, offset 89500
specimens.number_of_samples 131 from source
ENA sample_count=131

Section ENA study report, offset —
specimens.participant_to_sample_mapping_available True
across the four samples originating from each CD patient and across the two samples originating from each healthy, non-CD subject

Section Bioinformatic processing of shotgun sequencing samples, offset 113000
specimens.sample_type mixed
Paired involved and adjacent uninvolved ileal segments... with attached CrF and adjacent uninvolved mesenteric adipose... and blood

Section Results—Metagenomic Sequencing Reveals Bacterial Translocation, offset 8300