Gastrointestinal Surgery for Inflammatory Bowel Disease Persistently Lowers Microbiome and Metabolome Diversity
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Gastrointestinal Surgery for Inflammatory Bowel Disease Persistently Lowers Microbiome and Metabolome Diversity.
Abstract
<h4>Background</h4>Many studies have investigated the role of the microbiome in inflammatory bowel disease (IBD), but few have focused on surgery specifically or its consequences on the metabolome that may differ by surgery type and require longitudinal sampling. Our objective was to characterize and contrast microbiome and metabolome changes after different surgeries for IBD, including ileocolonic resection and colectomy.<h4>Methods</h4>The UC San Diego IBD Biobank was used to prospectively collect 332 stool samples from 129 subjects (50 ulcerative colitis; 79 Crohn's disease). Of these, 21 with Crohn's disease had ileocolonic resections, and 17 had colectomies. We used shotgun metagenomics and untargeted liquid chromatography followed by tandem mass spectrometry metabolomics to characterize the microbiomes and metabolomes of these patients up to 24 months after the initial sampling.<h4>Results</h4>The species diversity and metabolite diversity both differed significantly among groups (species diversity: Mann-Whitney U test P value = 7.8e-17; metabolomics, P-value = 0.0043). Escherichia coli in particular expanded dramatically in relative abundance in subjects undergoing surgery. The species profile was better able to classify subjects according to surgery status than the metabolite profile (average precision 0.80 vs 0.68).<h4>Conclusions</h4>Intestinal surgeries seem to reduce the diversity of the gut microbiome and metabolome in IBD patients, and these changes may persist. Surgery also further destabilizes the microbiome (but not the metabolome) over time, even relative to the previously established instability in the microbiome of IBD patients. These long-term effects and their consequences for health outcomes need to be studied in prospective longitudinal trials linked to microbiome-involved phenotypes.
Study facts
- Organism
- —
- Platform
- HiSeq 4000
- Age group
- —
- Disease groups
- Crohn's disease, Ulcerative colitis
- Anatomical sites
- —
Data availability
- Analysis code
Strengths & limitations for reuse
Strengths
- Raw reads are advertised
- Analysis code is available
- Participant counts are documented
- Sample counts are documented
Limitations
- Not documented: feature/otu tables are advertised
- 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.platform |
HiSeq 4000 |
sequenced using HiSeq 4000 platform. Section |
assay.sequencing_type |
shotgun_metagenomics |
we perform deep-coverage shotgun metagenomics Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.crohns_disease_participants |
79 |
332 stool samples from 129 subjects (50 ulcerative colitis 79 Crohn’s disease). Section |
cohort.disease_activity_metadata_available |
True |
We separated samples into those from patients with active endoscopic disease vs inactive endoscopic disease activity. Section |
cohort.study_design |
longitudinal |
Stool samples for each subject were collected approximately every 6 months. Section |
cohort.total_participants |
129 |
The UC San Diego IBD Biobank was used to prospectively collect 332 stool samples from 129 subjects (50 ulcerative colitis 79 Crohn’s disease). Section |
cohort.treatment_exposure_documented |
True |
95 (73.6%) patients have current or prior TNF inhibitor exposure. Section |
cohort.treatment_response_metadata_available |
True |
We did not identify differences based on response to TNF-inhibitors with and without stratifying based on prior surgery. Section |
cohort.ulcerative_colitis_participants |
50 |
332 stool samples from 129 subjects (50 ulcerative colitis 79 Crohn’s disease). Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.analysis_code |
True |
A detailed description of the individual steps has been published as a collection of Jupyter notebooks Section |
data_assets.open_access |
True from source |
"isOpenAccess": "Y" Section |
data_assets.pipeline_or_tool_versions |
True |
MetaPhlan2 2.7.7 ... HUMAnN2 0.11.2 Section |
data_assets.qc_or_negative_controls_reported |
True |
we trimmed the adaptors and performed quality filtering ... and filtered out host reads Section |
data_assets.raw_reads |
True |
The metagenomic sequencing data have been deposited to the European Bioinformatics Institute (EBI accession is ERP121770) Section |
data_assets.sample_metadata |
True |
the full data set including sample metadata has been made public on Qiita Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.body_site |
gut inferred |
Participants collected samples at home in Covidien 2450SA stool specimen containers. Section |
specimens.inflamed_status_available |
True |
active endoscopic disease vs inactive endoscopic disease activity Section |
specimens.longitudinal_sampling |
True |
Stool samples for each subject were collected approximately every 6 months. Section |
specimens.number_of_samples |
300 |
After filtering out low-quality samples, we worked with 300 metagenomics samples. Section |
specimens.sample_type |
stool |
Participants collected samples at home in Covidien 2450SA stool specimen containers. Section |