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

Dataset overview

Participants 28

Samples 131

Reuse readiness 8.0/10 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
Participant-to-sample mapping is available
Participant counts are documented
Sample counts are documented

Limitations

Not documented: taxonomic tables are advertised

Extraction evidence & provenance

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

Assay

Field	Value	Evidence
`assay.paired_end`	True	paired-end 2x150bp sequencing Section `STAR Methods—DNA extraction and library preparation for deep shotgun sequencing`, offset 67000
`assay.platform`	Illumina NovaSeq 6000	paired-end 2x150bp sequencing using a S4 flow cell of a NovaSeq 6000 instrument Section `STAR Methods—DNA extraction and library preparation for deep shotgun sequencing`, offset 67000
`assay.read_length`	150	paired-end 2x150bp sequencing Section `STAR Methods—DNA extraction and library preparation for deep shotgun sequencing`, offset 67000
`assay.sequencing_type`	shotgun_metagenomics	We performed deep shotgun metagenomic sequencing Section `Results—Metagenomic Sequencing`, offset 8500

Cohort

Field	Value	Evidence
`cohort.age_group`	adult inferred	Exclusion criteria included patients under 18 Section `STAR Methods—Human subjects`, offset 59000
`cohort.crohns_disease_participants`	11	were obtained from 11 patients undergoing surgical resections due to complications from CD. Section `Results—Metagenomic Sequencing`, offset 7600
`cohort.non_ibd_controls`	4	healthy tissue controls ... from four subjects Section `Results—Metagenomic Sequencing`, offset 7950
`cohort.study_design`	cross_sectional inferred	patients undergoing surgical resections ... collected ... controls Section `Results—Metagenomic Sequencing`, offset 7600
`cohort.total_participants`	28 computed	11 patients ... 13 UC patients ... healthy tissue controls ... from four subjects Section `Results—Metagenomic Sequencing`, offset 7600
`cohort.treatment_exposure_documented`	True	Patient metadata including clinical characteristics, medication use ... are detailed in Table S1. Section `Results—Metagenomic Sequencing`, offset 8200
`cohort.ulcerative_colitis_participants`	13	we collected the analogous regions ... from 13 UC patients as controls Section `Results—Metagenomic Sequencing`, offset 7800

Data_Assets

Field	Value	Evidence
`data_assets.feature_or_otu_table`	True	the data were saved as a biom table for later processing in QIIME 2 Section `STAR Methods—Bioinformatic processing of shotgun sequencing samples`, offset 70000
`data_assets.open_access`	True from source	isOpenAccess: "Y" Section `Publication metadata`, offset —
`data_assets.pipeline_or_tool_versions`	True	processed by SHOGUN ... Woltka ... QIIME 2 Section `STAR Methods—Bioinformatic processing of shotgun sequencing samples`, offset 69000
`data_assets.qc_or_negative_controls_reported`	True	a total of four negative control blanks were processed alongside the samples Section `STAR Methods—DNA extraction and library preparation for deep shotgun sequencing`, offset 67500
`data_assets.raw_reads`	True	The accession number for the microbial sequencing files reported in this paper is BioProject: PRJNA659515. Section `Data Availability Statement`, offset 101000

Specimens

Field	Value	Evidence
`specimens.body_site`	mesenteric adipose tissue and intestinal mucosa	both adipose and intestinal samples were submitted for histology Section `STAR Methods—Tissue Collection`, offset 63500
`specimens.inflamed_status_available`	True	involved and adjacent uninvolved ileal segments Section `Results—Metagenomic Sequencing`, offset 7600
`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 Section `STAR Methods—Bioinformatic processing`, offset 73000
`specimens.sample_type`	mixed	paired involved and adjacent uninvolved ileal segments ... with attached CrF and adjacent uninvolved mesenteric adipose Section `Results—Metagenomic Sequencing`, offset 7600