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PRJNA999593 SRP451949

Fecal metagenome in non-cirrhotic NASH vs controls, USA

An integrated analysis of fecal microbiome and metabolomic features distinguish Non-cirrhotic NASH from healthy control populations

Case-control study of 307 fecal samples from US adults, comparing biopsy-proven non-cirrhotic NASH (F1-F3 fibrosis) patients to healthy controls using shotgun metagenomics and fecal bile acid metabolomics. machine-written summary

307 samples · 307 runs · US · Adult · 2023 · 3.05 Gbp / sample

Sources
✓Sequence archive 1,535○Abstract / description○Full text–Supplementary tables✓External resources 558–User contribution–Human verified

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

what each source gave
✓ Sequence archive1,535 sample values (country, latitude, location region, longitude, subject id)
○ Abstract / descriptionread; no usable statement
○ Full textread; no usable statement or table · PMC10674038
– Supplementary tablesno supplementary tables available (or none open access)
✓ External resources558 sample values (health condition, health condition detail) · 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
adult307
Condition
cardiometabolic_other279
Country
US307
Body site
primary279
unknown28
Sequencing depth per sample · this project all projects
all projects, 0–0.03 Gbp: 25,080 samples (4 %)this project, 0–0.03 Gbp: 21 samplesall 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 %)this project, 0.3–1 Gbp: 6 samplesall projects, 1–3 Gbp: 124,983 samples (22 %)this project, 1–3 Gbp: 123 samplesall projects, 3–10 Gbp: 253,728 samples (44 %)this project, 3–10 Gbp: 157 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 3.05 Gbp per sample0130Gbp
Community composition
Bacteroides 16.3%Phocaeicola 7.9%Escherichia 3.8%Alistipes 3.7%Roseburia 3.6%Enterocloster 3.5%Blautia_A 3.5%Akkermansia 3.0%Faecalibacterium 2.9%Vibrio 2.6%Prevotella 2.6%Parabacteroides 2.0%not assigned to a genus 6.9%other genera 37.8%

Genera, mean relative abundance over 260 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).

Field coverage
fieldsamplescoverageR1R2R3R4
age_category307 100%
country307 100%307
health_condition279 91%279
subject_id307 100%307
detailed_location307 100%
latitude307 100%307
location_region307 100%307
longitude307 100%307
health_condition_detail279 91%279
Papers (1)
  • An integrated analysis of fecal microbiome and metabolomic features distinguish non-cirrhotic NASH from healthy control populations. 2023 PMID 37222264 PMC10674038 own_data
Details
Archive description

There is great interest in identifying microbiome features as reliable noninvasive diagnostic and/or prognostic biomarkers for non-cirrhotic NASH fibrosis. Several cross-sectional studies have reported gut microbiome features associated with advanced NASH fibrosis and cirrhosis, where the most prominent features are associated with cirrhosis. However, no large, prospectively collected data exist establishing microbiome features that discern non-cirrhotic NASH fibrosis, integrate the fecal metabolome as disease biomarkers, and are unconfounded by BMI and age. Results from shotgun metagenomic sequencing performed on fecal samples prospectively collected from 279 US patients with biopsy-proven NASH (F1-F3 fibrosis) enrolled in the REGENERATE I303 study were compared to those from three healthy control cohorts and integrated with the absolute quantification of fecal bile acids. Microbiota beta-diversity was different, and BMI- and age-adjusted logistic regression identified 12 NASH-associated species. Random forest prediction models resulted in an AUC of 0.75 to 0.81 in a receiver operator characteristic analysis. Additionally, specific fecal bile acids were significantly lower in NASH and correlated with plasma C4 levels. Microbial gene abundance analysis revealed 127 genes increased in controls, many involving protein synthesis, whereas 362 genes were increased in NASH many involving bacterial environmental responses (FDR < 0.01). Finally, we provide evidence that fecal bile acid levels may be a better discriminator of non-cirrhotic NASH versus health than either plasma bile acids or gut microbiome features. These results may have value as a set of baseline characteristics of non-cirrhotic NASH against which therapeutic interventions to prevent cirrhosis can be compared and microbiome-based diagnostic biomarkers identified.

How this project entered the registry

Classified as human gut / stool / blood / tissue / internal fluids shotgun DNA metagenome of adult by deterministic_prior with confidence 0.90. Assay shotgun_dna.

  • host external_curation.infant_catalog · “infant triage reason_code age_adult_only”
  • body site study.title · “integrated analysis of fecal microbiome and metabolomic”
  • body site study.description · “studies have reported gut microbiome features associated”
  • body site study.description · “US patients with biopsy -proven NASH (F1-F3”
  • life stage external_curation.infant_catalog · “infant triage reason_code age_adult_only”
Evidence examples (one per field × route)
samplefieldvaluerouteconf.sourcequote
SAMN36736951countryUSR10.90sample.attr.geo_loc_nameUSA
SAMN36736979health_conditioncardiometabolic_otherR20.75external.gmrepo sourcephenotype: Non-alcoholic Fatty Liver Disease
SAMN36736979health_condition_detailNon-alcoholic Fatty Liver DiseaseR20.75external.gmrepo sourcephenotype: Non-alcoholic Fatty Liver Disease
SAMN36736951latitude39.9473R10.90biosample.attribute:lat_lon39.9473 N 75.1958 W
SAMN36736951location_regionPennsylvaniaR10.60biosample.attribute:lat_lon39.9473 N 75.1958 W
SAMN36736951longitude-75.1958R10.90biosample.attribute:lat_lon39.9473 N 75.1958 W
SAMN36736951subject_idVibriolambda7R10.85sample.attr.subject_idVibriolambda7
Sequencing

307 runs over 307 samples · mean 2.96 Gbp per run (median 3.05 Gbp, total 907.48 Gbp; 307 runs with a base count) · layout PAIRED 307 · platform ILLUMINA 307 · models Illumina HiSeq 2500 (307) · 85% of runs with a Sandpiper profile · first public 2023-07-29

Authors (0)

No author record.

Downloads

PRJNA999593.csv.gz (8.6 KB) · parquet (82.7 KB) — all 307 samples, every field with route and confidence · PRJNA999593_determinations.csv.gz (14.9 KB) — 2,093 evidence rows

Samples (307 · every field this project has values for · hover a cell for its source)
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