Metagenomic Analysis of Common Intestinal Diseases Reveals Relationships among Microbial Signatures and Powers Multidisease Diagnostic Models

Study information

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-7

study design

case-control
meta-analysis

Citation

PMID PubMed identifier for scientific articles.

33947803

DOI Digital object identifier for electronic documents.

10.1128/mSystems.00112-21

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269207/

Authors

Jiang P, Wu S, Luo Q, Zhao XM, Chen WH

Journal

mSystems

Year

2021

Keywords:

gut dysbiosis, human microbiome, intestinal disease, machine learning-based disease classification, noninvasive disease diagnosis

Common intestinal diseases such as Crohn's disease (CD), ulcerative colitis (UC), and colorectal cancer (CRC) share clinical symptoms and altered gut microbes, necessitating cross-disease comparisons and the use of multidisease models. Here, we performed meta-analyses on 13 fecal metagenome data sets of the three diseases. We identified 87 species and 65 pathway markers that were consistently changed in multiple data sets of the same diseases. According to their overall trends, we grouped the disease-enriched marker species into disease-specific and disease-common clusters and revealed their distinct phylogenetic relationships; species in the CD-specific cluster were phylogenetically related, while those in the CRC-specific cluster were more distant. Strikingly, UC-specific species were phylogenetically closer to CRC, likely because UC patients have higher risk of CRC. Consistent with their phylogenetic relationships, marker species had similar within-cluster and different between-cluster metabolic preferences. A portion of marker species and pathways correlated with an indicator of leaky gut, suggesting a link between gut dysbiosis and human-derived contents. Marker species showed more coordinated changes and tighter inner-connections in cases than the controls, suggesting that the diseased gut may represent a stressed environment and pose stronger selection on gut microbes. With the marker species and pathways, we constructed four high-performance (including multidisease) models with an area under the receiver operating characteristic curve (AUROC) of 0.87 and true-positive rates up to 90%, and explained their putative clinical applications. We identified consistent microbial alterations in common intestinal diseases, revealed metabolic capacities and the relationships among marker bacteria in distinct states, and supported the feasibility of metagenome-derived multidisease diagnosis.IMPORTANCE Gut microbes have been identified as potential markers in distinguishing patients from controls in colorectal cancer, ulcerative colitis, and Crohn's disease individually, whereas there lacks a systematic analysis to investigate the exclusive microbial shifts of these enteropathies with similar clinical symptoms. Our meta-analysis and cross-disease comparisons identified consistent microbial alterations in each enteropathy, revealed microbial ecosystems among marker bacteria in distinct states, and demonstrated the necessity and feasibility of metagenome-based multidisease classifications. To the best of our knowledge, this is the first study to construct multiclass models for these common intestinal diseases.

Experiment 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-7

Curated date: 2022/01/21

Curator: Itslanapark

Revision editor(s): Itslanapark, WikiWorks, Peace Sandy

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Colorectal carcinoma

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Non disease controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: CRC patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with colorectal cancer

Group 0 sample size Number of subjects in the control (unexposed) group: 632

Group 1 sample size Number of subjects in the case (exposed) group: 354

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Signature 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-7

Curated date: 2022/01/24

Curator: Itslanapark

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Source: Figure 1

Description: Disease-specific and shared microbial markers showed distinct prevalence profiles in patients and controls. (A) Microbial markers and their trends (i.e., case- or control-enriched) in common intestinal diseases. Species significantly enriched in cases (or controls) of corresponding disease in meta-analysis are shown (fdr < 0.05 in meta-analysis, Benjamini-Hochberg FDR correction), with their phylum shown on top. Red indicates case-enriched species and blue indicates control-enriched ones.

Abundance in Group 1: decreased abundance in CRC patients

NCBI	Quality Control	Links
Anaerobutyricum hallii
Anaerostipes hadrus
Coprococcus comes
Lachnospiraceae bacterium 5_1_63FAA
Roseburia intestinalis
Bifidobacterium adolescentis
Bacteroides nordii
Phocaeicola plebeius
Bacteroides stercoris
Bacteroidales bacterium
Odoribacter laneus
Parabacteroides goldsteinii
Alistipes putredinis
Alistipes senegalensis
Alistipes shahii
Bacteroides cellulosilyticus
Bacteroides thetaiotaomicron
[Clostridium] leptum
[Bacteroides] pectinophilus
[Eubacterium] siraeum
Eubacterium ventriosum
Coprococcus catus
Roseburia hominis
Roseburia inulinivorans
[Ruminococcus] lactaris
[Clostridium] symbiosum
Lachnospiraceae bacterium
Ruminococcus bromii
Subdoligranulum
Megamonas hypermegale
Megamonas

Revision editor(s): Itslanapark, Peace Sandy, WikiWorks

Signature 2

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Curated date: 2022/01/25

Curator: Itslanapark

Revision editor(s): WikiWorks, Itslanapark, Aiyshaaaa, Peace Sandy

Source: Figure 1

Description: Disease-specific and shared microbial markers showed distinct prevalence profiles in patients and controls. (A) Microbial markers and their trends (i.e., case- or control-enriched) in common intestinal diseases. Species significantly enriched in cases (or controls) of corresponding disease in meta-analysis are shown (fdr < 0.05 in meta-analysis, Benjamini-Hochberg FDR correction), with their phylum shown on top. Red indicates case-enriched species and blue indicates control-enriched ones.

Abundance in Group 1: increased abundance in CRC patients

NCBI	Quality Control	Links
Alistipes ihumii AP11
Alistipes onderdonkii
Alloprevotella tannerae
Anaerotruncus colihominis
Anaerotruncus sp.
Bacteroides fragilis
Bacteroides salyersiae
Bilophila wadsworthia
Clostridiales bacterium 1_7_47FAA
Desulfovibrio desulfuricans
Enterocloster asparagiformis
Enterocloster bolteae
Enterocloster citroniae
Erysipelotrichaceae bacterium 2_2_44A
Fusobacterium nucleatum
Gemella morbillorum
Granulicatella adiacens
Hungatella hathewayi
Lachnospiraceae bacterium 3_1_57FAA_CT1
Lachnospiraceae bacterium 7_1_58FAA
Megasphaera sp.
Parvimonas micra
Parvimonas sp.
Peptostreptococcus anaerobius
Peptostreptococcus sp.
Peptostreptococcus stomatis
Porphyromonas asaccharolytica
Porphyromonas somerae
Porphyromonas uenonis
Prevotella intermedia
Ruminococcaceae bacterium D16
Slackia sp.
Solobacterium moorei
Streptococcus anginosus
Subdoligranulum sp. 4_3_54A2FAA
Synergistes sp. 3_1_syn1
[Clostridium] innocuum
[Clostridium] symbiosum
[Ruminococcus] torques
Alistipes finegoldii
Alistipes sp.
Streptococcus parasanguinis
Streptococcus oralis
Ruminococcus
Anaerostipes hadrus
Clostridiales bacterium
Anaerococcus vaginalis
Flavonifractor plautii
Mediterraneibacter gnavus
Veillonella atypica
Veillonella
Megasphaera
Citrobacter freundii
Citrobacter sp.
Escherichia coli
Klebsiella oxytoca
Klebsiella sp.
Synergistes

Revision editor(s): WikiWorks, Itslanapark, Aiyshaaaa, Peace Sandy