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PRJNA373879 SRP116039

Fecal metagenomes and irinotecan metabolism, New York adults

Healthy human fecal metagenomes variably reactivate Irinotecan active metabolite

Cross-sectional study of 20 fecal metagenome samples from adults in New York (17 healthy control, 3 obesity), examining gut microbiota β-glucuronidase activity and inter-individual variability in reactivating irinotecan's inactive metabolite. machine-written summary

20 samples · 20 runs · US · Age unknown · 2017 · 3.62 Gbp / sample

Sources
✓Sequence archive 100○Abstract / description✓Full text 81○Supplementary tables✓External resources 79–User contribution–Human verified

Checked this project's papers and archive records yourself? Mark it human-verified.

what each source gave
✓ Sequence archive100 sample values (collection date, country, latitude, location region, longitude)
○ Abstract / descriptionread; no usable statement
✓ Full text81 sample values (antibiotic exposure, health condition, location locality, location site, subject id) · PMC5665930
○ Supplementary tablesfiles read; no table could be matched to the samples
✓ External resources79 sample values (age, health condition, health condition detail, sex) · from GMrepo v3
– User contributionnothing uploaded yet
– Human verifiednot yet checked by a person · I checked this project — verify it
Samples at a glance
1 sampling locations · 1 country
Age
adult20
Condition
healthy_control17
obesity3
Sex
female12
male8
Country
US20
Body site
primary20
Sequencing depth per sample · this project all projects
all projects, 0–0.03 Gbp: 25,080 samples (4 %)all projects, 0.03–0.1 Gbp: 17,066 samples (3 %)all projects, 0.1–0.3 Gbp: 29,179 samples (5 %)all projects, 0.3–1 Gbp: 47,044 samples (8 %)all projects, 1–3 Gbp: 124,983 samples (22 %)this project, 1–3 Gbp: 2 samplesall projects, 3–10 Gbp: 253,728 samples (44 %)this project, 3–10 Gbp: 18 samplesall projects, 10–30 Gbp: 72,533 samples (13 %)all projects, 30–100 Gbp: 3,024 samples (1 %)all projects, 100–300 Gbp: 106 samples (0 %)all projects, ≥ 300 Gbp: 9 samples (0 %)project median 3.62 Gbp per sample0130Gbp
Community composition
Bacteroides 22.4%Phocaeicola 15.2%Alistipes 6.7%Blautia_A 3.7%Roseburia 2.7%Faecalibacterium 2.7%Anaerostipes 2.0%Mediterraneibacter 1.7%Parabacteroides 1.7%Zag111 1.6%Lachnospira 1.6%Akkermansia 1.4%not assigned to a genus 6.1%other genera 30.5%

Genera, mean relative abundance over 15 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).

Field coverage
fieldsamplescoverageR1R2R3R4
age_category20 100%
country20 100%20
health_condition20 100%191
subject_id20 100%20
age_at_collection_days20 100%20
antibiotic_exposure20 100%20
collection_date20 100%20
detailed_location20 100%
health_condition_detail20 100%20
latitude20 100%20
location_locality20 100%20
location_region20 100%20
location_site20 100%20
longitude20 100%20
sex20 100%20
Papers (1)
  • Human microbiome signatures of differential colorectal cancer drug metabolism. 2017 PMID 29104759 PMC5665930 own_data
Details
Archive description

It is well appreciated that metabolism of irinotecan by the gut microbiota can influence efficacy and potentially produce patient-specific adverse drug responses. However, a direct connection between irinotecan metabollism and the composition of an individual’s gut microbiota has not previously been made. Here, we report the first quantitative evidence of inter-individual variability in microbiome metabolism of the inactive metabolite of irinotecan, a first-line chemotherapeutic for metastatic colorectal cancer, to its active form. We identify a high turnover microbiota metabotype with potentially elevated risk for irinotecan-dependent adverse drug responses. We link the high turnover metabotype to previously unreported microbial β-glucuronidases and suggest that inhibiting these enzymes therapeutically may decrease irinotecan-dependent adverse drug responses in targeted subsets of patients. In total, this study demonstrates that metagenomic mining of the microbiome, when combined with metabolomics, defines a non-invasive approach to develop biomarkers for colorectal cancer treatment outcomes.

How this project entered the registry

Classified as human gut / stool shotgun DNA metagenome of age unknown by sonnet_x2 with confidence 0.70. Assay shotgun_dna.

  • host run.scientific_name · “human metagenome”
  • host study.title · “Healthy human fecal metagenomes”
  • body site study.title · “human fecal metagenomes”
Evidence examples (one per field × route)
samplefieldvaluerouteconf.sourcequote
SAMN06220509age_at_collection_days9131.25R20.75external.gmrepo sourcehost_age: 25.0
SAMN06220509antibiotic_exposurenoR30.70paper.fulltext.methodshad not used antibiotics within the prior 6 months
SAMN06220509collection_date2015-07-07R10.90biosample.attribute:collection_date2015-07-07
SAMN06220509countryUSR10.90sample.attr.geo_loc_nameUSA: New York
SAMN06220509health_conditionhealthy_controlR20.75external.gmrepo sourcephenotype: Health
SAMN07534319health_conditionhealthy_controlR30.70paper.fulltext.methods20 healthy individuals were recruited
SAMN06220509health_condition_detailHealthR20.75external.gmrepo sourcephenotype: Health
SAMN06220509latitude40.7128R10.90biosample.attribute:lat_lon40.7128 N 74.0059 W
SAMN06220509location_localityBronxR30.70paper.fulltext.methodsSubjects were recruited via flyers posted at Albert Einstein College of Medicine
SAMN06220509location_regionNew YorkR10.85biosample.attribute:geo_loc_nameUSA: New York
SAMN06220509location_siteAlbert Einstein College of MedicineR30.70paper.fulltext.methodsSubjects were recruited via flyers posted at Albert Einstein College of Medicine
SAMN06220509longitude-74.0059R10.90biosample.attribute:lat_lon40.7128 N 74.0059 W
SAMN06220509sexfemaleR20.75external.gmrepo sourcesex: Female
SAMN06220509subject_idSAMN06220509R30.70design.one_sample_per_subject:fulltextFecal samples were collected from 20 healthy individuals; details of the cohort are provided in Table S1
Sequencing

20 runs over 20 samples · mean 3.59 Gbp per run (median 3.62 Gbp, total 71.86 Gbp; 20 runs with a base count) · layout PAIRED 20 · platform ILLUMINA 20 · models Illumina HiSeq 2500 (20) · 75% of runs with a Sandpiper profile · first public 2017-11-09

Authors (21)

Guthrie L first · Gupta S · Daily J · Kelly L last · Argentini C first · Lugli GA · Tarracchini C · Fontana F · Mancabelli L · Viappiani A · Anzalone R · Angelini L · Alessandri G · Longhi G · Bianchi MG · Taurino G · Bussolati O · Milani C · van Sinderen D · Turroni F · Ventura M last

Downloads

PRJNA373879.csv.gz (1.7 KB) · parquet (72.2 KB) — all 20 samples, every field with route and confidence · PRJNA373879_determinations.csv.gz (3.4 KB) — 260 evidence rows

Samples (20 · every field this project has values for · hover a cell for its source)
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