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

Dataset overview

Participants None

Samples None

Reuse readiness 5.6/10 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: Homo sapiens
Platform: SureCell and Chromium
Age group: adult
Disease groups: —
Anatomical sites: —

Data availability

Analysis code

Strengths & limitations for reuse

Strengths

Raw reads are advertised
Feature/OTU tables are advertised
Analysis code is available

Limitations

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

Field Value Evidence

Field	Value	Evidence
`assay.platform`	SureCell and Chromium	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`, offset —
`assay.read_depth_reported`	175000	sequenced on the Illumina NextSeq platform at an average read depth of 175,000 reads/sample Section `CrF versus CD MAT and UC MAT`, offset —

assay.platform

SureCell and Chromium

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, offset —

assay.read_depth_reported

175000

sequenced on the Illumina NextSeq platform at an average read depth of 175,000 reads/sample

Section CrF versus CD MAT and UC MAT, offset —

Cohort

Field Value Evidence

Field	Value	Evidence
`cohort.age_group`	adult	Exclusion criteria included patients under 18 Section `Experimental Model and Subject Details > Human subjects`, offset 1012000
`cohort.study_design`	cross_sectional inferred	were obtained from 11 patients undergoing surgical resections Section `Results > Metagenomic Sequencing Reveals Bacterial Translocation`, offset 8200
`cohort.treatment_exposure_documented`	True	Patient metadata including clinical characteristics, medication use, family history, social history, and demographic information ... are detailed in Table S1. Section `Results`, offset 5200

cohort.age_group

adult

Exclusion criteria included patients under 18

Section Experimental Model and Subject Details > Human subjects, offset 1012000

cohort.study_design

cross_sectional inferred

were obtained from 11 patients undergoing surgical resections

Section Results > Metagenomic Sequencing Reveals Bacterial Translocation, offset 8200

cohort.treatment_exposure_documented

True

Patient metadata including clinical characteristics, medication use, family history, social history, and demographic information ... are detailed in Table S1.

Section Results, offset 5200

Data_Assets

Field	Value	Evidence
`data_assets.analysis_code`	True	scRNA-seq codes are available on Github (https://github.com/DevkotaLab/ha-et-al-2020-cell). Section `STAR Methods > Data and Code Availability`, offset 69000
`data_assets.feature_or_otu_table`	True	The filtered count matrices generated by Cell Ranger were used as input. Section `STAR Methods > 10X Genomics Cell Ranger sample processing`, offset 65000
`data_assets.open_access`	True from source	"isOpenAccess": "Y" Section `publication metadata`, offset —
`data_assets.pipeline_or_tool_versions`	True	Cell counts were generated using the 10X Genomics Cell Ranger v3.1.0 pipeline Section `STAR Methods > 10X Genomics Cell Ranger sample processing`, offset 65000
`data_assets.raw_reads`	True	All of the DNA and RNA sequencing datasets generated in this study have been deposited to NCBI. Section `STAR Methods > Data and Code Availability`, offset 42000

Specimens

Field Value Evidence

Field	Value	Evidence
`specimens.body_site`	mesenteric adipose tissue inferred	Single-cell RNA-seq analysis of stromal vascular cells (SVCs) isolated from primary adipose tissue. Section `study`, offset —

specimens.body_site

mesenteric adipose tissue inferred

Single-cell RNA-seq analysis of stromal vascular cells (SVCs) isolated from primary adipose tissue.

Section study, offset —