Foundry120 atlas

← IBD microbiome

Gut microbial factors implicated in disease progression and treatment response in pediatric ulcerative colitis

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Dataset overview

Participants None
Samples 1,453
Reuse readiness 6.4/10 evidence-backed score

Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response.

Haberman Y, Karns R, Dexheimer PJ, Schirmer M, Somekh J, Jurickova I, Braun T, Novak E, et al. · Nature communications · 2019

Abstract

Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α<sub>4</sub>β<sub>7</sub> integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.

doi:10.1038/s41467-018-07841-3 ↗ PMID 30604764 ↗ PMC6318335 ↗

Study facts

Organism
—
Platform
Illumina HiSeq 2500
Age group
paediatric
Disease groups
—
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
  • Sample counts are documented

Limitations

  • 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 Illumina HiSeq 2500
"instrument_model": "Illumina HiSeq 2500"

Section ena_study, offset 1300
assay.sequencing_type shotgun_metagenomics
"library_source": "METAGENOMIC", "library_strategy": "WGS"

Section ena_study, offset 1450

Cohort

FieldValueEvidence
cohort.age_group paediatric
This project collected and profiled stool samples and rectal biopsies from pediatric patients with new-onset ulcerative colitis (UC)

Section ena_study, offset 1000
cohort.disease_activity_metadata_available True
Clinical activity at diagnosis was established with the PUCAI ... Mayo endoscopic scope ... and total Mayo score

Section Methods—Study design and participants, offset 43800
cohort.treatment_exposure_documented True
Depending on initial PUCAI score, patients received initial treatment with either mesalamine (mild disease), or corticosteroids (moderate and severe disease)

Section Methods—Study design and participants, offset 46500
cohort.treatment_response_metadata_available True
152 of the 206 UC patients in our cohort also had fecal 16S rRNA microbial profiles

Section Results—Corticosteroid response gene signature and microbial shifts, offset 19000

Data_Assets

FieldValueEvidence
data_assets.feature_or_otu_table True
for the OTU analysis the 16S bioBakery workflow ... was applied

Section Methods—Microbiome analyses, offset 57000
data_assets.open_access True
"isOpenAccess": "Y"

Section europepmc_record, offset —
data_assets.pipeline_or_tool_versions True
the 16S bioBakery workflow built with AnADAMA2 ... microbial taxonomy was based on the Greengenes 16S rDNA database (version 13.5)

Section Methods—Microbiome analyses, offset 57000
data_assets.raw_reads True
"run_count": 1453, "runs_sample": [{"run_accession": "SRR27217289"

Section ena_study, offset 1180
data_assets.taxonomic_table True
microbial taxonomy was based on the Greengenes 16S rDNA database (version 13.5)

Section Methods—Microbiome analyses, offset 57150

Specimens

FieldValueEvidence
specimens.body_site stool and rectum
This project collected and profiled stool samples and rectal biopsies

Section ena_study, offset 1000
specimens.inflamed_status_available True
A central pathologist blinded to clinical data examined a single rectal biopsy from each patient and assessed histological features of chronicity and quantitated acute inflammation.

Section Methods—Study design and participants, offset 44000
specimens.number_of_samples 1453 from source
ENA sample_count=1453

Section ENA study report, offset —
specimens.sample_type mixed
This project collected and profiled stool samples and rectal biopsies

Section ena_study, offset 1000