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

Study information

Needs review

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 Uniform resource identifier for web resources.

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

Authors

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

Journal

mSystems

Year

2021

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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Curated date: 2022/01/21

Curator: Itslanapark

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Subjects

Host species Species from which microbiome was sampled (if applicable): 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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: colorectal cancer cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine

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

Statistical Analysis

Statistical test: Kruskall-Wallis; Mann-Whitney (Wilcoxon); Chi-Square

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): .05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

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

Signature 1

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Curated date: 2022/01/24

Curator: Itslanapark

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Source: Figure 1

Description: microbial markers and their trends in controls and crc patients

Abundance in Group 1: decreased abundance in CRC patients

NCBI	Links
Anaerobutyricum hallii
Anaerostipes hadrus
Lachnospiraceae bacterium 5_1_63FAA
Coprococcus comes
Roseburia intestinalis

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Signature 2

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Curated date: 2022/01/25

Curator: Itslanapark

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Source: Figure 1

Description: microbial markers and their trends in controls and crc patients

Abundance in Group 1: increased abundance in CRC patients

NCBI	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
[Clostridium] innocuum ⚠
[Clostridium] symbiosum
[Ruminococcus] torques
Synergistes sp. 3_1_syn1

Revision editor(s): Itslanapark, Aiyshaaaa