Fecal bacterial biomarkers and blood biochemical indicators as potential key factors in the development of colorectal cancer

Study information

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

40013832

DOI Digital object identifier for electronic documents.

10.1128/msystems.00043-25

URI

https://pmc.ncbi.nlm.nih.gov/articles/PMC11915818/

Authors

Cai P, Yang Q, Lu J, Dai X, Xiong J

Journal

mSystems

Year

2025

Keywords:

blood biochemical indicators, colorectal cancer, fecal microbiome, polyps, random forest model

UNLABELLED: The incidence of colorectal cancer (CRC) has been increasing in recent decades. Current methods for CRC screening have their own drawbacks, thus there is an urgent need to identify the key microbes that drive the development of CRC for wider application in the early detection and prevention of CRC. To address this issue, we performed fecal microbiome analysis by high-throughput sequencing of 16S rRNA gene combined with blood biochemical indicators in patients with CRC stages I, II, III, and IV, healthy people, and patients with polyps. Fecal microbiota of patients with CRC was disturbed, as evidenced by significantly reduced α-diversity in patients with CRC stage IV and markedly different β-diversity. The random forest model identified the top 25 genera from 174 training data, resulting in a diagnostic accuracy of 87.95%. Further, by combining with differential genera analysis, we screened out 11 biomarkers that significantly changed in different groups. Peptostreptococcus, Parvimonas, Shewanella, Oscillibacter, Eggerthella, and Gemella associated with the development of CRC were significantly enriched, while Fenollaria, Staphylococcus, Ezakiella, Finegoldia, and Neisseria associated with the remission of CRC were significantly suppressed in patients with CRC. Importantly, carcinoembryonic antigen (CEA) was significantly correlated with these 11 microbial biomarkers, and carbohydrate antigen 19-9 (CA 19-9) was markedly correlated with Oscillibacter. Notably, co-occurrence network analysis at the genus level exhibited that the microbial co-occurrence network of CRC IV was the most complex and stable. These results suggested that CEA, CA 19-9 and 11 microbial biomarkers may be co-biomarkers for the disease occurrence and development, and non-invasive diagnosis of CRC. IMPORTANCE: Identifying the key microbes that drive the development of colorectal cancer (CRC) has been important in this field. We delved into the research on the association between CRC and fecal microbiota in this study, providing a detailed analysis of the characteristics of fecal microbiota during the transition from normal intestine to polyps to cancer. Fecal bacterial biomarkers and blood biochemical indicators may be co-biomarkers in the development of CRC.

Experiment 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/04

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Subjects

Location of subjects

China

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 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,Colorectal cancer

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Healthy Volunteers ( H group)

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

Colorectal Cancer stage I patients (C1 group)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagnosed with Colorectal Cancer stage I (C1)

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

120

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

35

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

1 Month

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Statistical test

ANOVA

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)?

No

Alpha Diversity

Richness Number of species

unchanged

Signature 1

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Curated date: 2025/04/04

Curator: Nithya

Revision editor(s): Nithya, Shulamite, KateRasheed

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant Phyla

Abundance in Group 1: increased abundance in Colorectal Cancer stage I patients (C1 group)

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Eggerthella
Gemella
Oscillibacter
Parvimonas
Peptostreptococcus
Fusobacteriota

Revision editor(s): Nithya, Shulamite, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/04

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Source: Figure 2C and Figure 4

Description: Boxplot analysis of key differential genera from diagnosis model and dominant Phyla

Abundance in Group 1: decreased abundance in Colorectal Cancer stage I patients (C1 group)

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Ezakiella
Fenollaria
Pseudomonadota

Revision editor(s): Nithya, Shulamite

Experiment 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Healthy Volunteers (H group)

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

Colorectal Cancer stage II patients (C2 group)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagnosed with Colorectal Cancer stage II (C2 group)

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

101

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species

increased

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite, KateRasheed

Source: Figure 2C and Figure 4

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: increased abundance in Colorectal Cancer stage II patients (C2 group)

NCBI	Quality Control	Links
Gemella
Parvimonas
Peptostreptococcus
Shewanella
Bacteroidota
Fusobacteriota

Revision editor(s): Nithya, Shulamite, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Source: Figure 2C and Figure 4

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: decreased abundance in Colorectal Cancer stage II patients (C2 group)

NCBI	Quality Control	Links
Ezakiella
Fenollaria
Neisseria
Pseudomonadota

Revision editor(s): Nithya, Shulamite

Experiment 3

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/04

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

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

Colorectal Cancer patients (CRC)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagnosed with Colorectal Cancer (CRC)

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

261

Lab analysis

Statistical Analysis

Statistical test

Random Forest Analysis

Signature 1

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Curated date: 2025/04/04

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Source: Figure 3A and 3B

Description: Relative abundance ratios of genera between the Cancer and Healthy groups

Abundance in Group 1: increased abundance in Colorectal Cancer patients (CRC)

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Catonella
Eggerthella
Gemella
Oscillibacter
Parvimonas
Peptostreptococcus
Shewanella

Revision editor(s): Nithya, Shulamite

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/07

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Source: Figure 3A and 3B

Description: Relative abundance ratios of genera between the Cancer and Healthy groups

Abundance in Group 1: decreased abundance in Colorectal Cancer patients (CRC)

NCBI	Quality Control	Links
Corynebacterium
Ezakiella
Fenollaria
Finegoldia
Neisseria
Peptoniphilus
Staphylococcus
Varibaculum

Revision editor(s): Nithya, Shulamite

Experiment 4

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

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

Colorectal Cancer stage III patients (C3 group)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagnosed with Colorectal Cancer stage III (C3 group)

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

110

Lab analysis

Statistical Analysis

Statistical test

ANOVA

Alpha Diversity

Richness Number of species

increased

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/09

Curator: Shulamite

Revision editor(s): Shulamite, Nithya, KateRasheed

Source: Figure 2C and Figure 4

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: increased abundance in Colorectal Cancer stage III patients (C3 group)

NCBI	Quality Control	Links
Eggerthella
Gemella
Parvimonas
Peptostreptococcus
Bacteroidota
Fusobacteriota

Revision editor(s): Shulamite, Nithya, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite, KateRasheed

Source: Figure 2C and Figure 4

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: decreased abundance in Colorectal Cancer stage III patients (C3 group)

NCBI	Quality Control	Links
Ezakiella
Fenollaria
Neisseria
Pseudomonadota
Staphylococcus

Revision editor(s): Nithya, Shulamite, KateRasheed

Experiment 5

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/10

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Patients with Polyps (P group)

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

Patients with Colorectal Cancer stage I (C1)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagonosed with Colorectal Cancer stage I (C1)

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

92

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

35

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species

decreased

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/10

Curator: Nithya

Revision editor(s): Nithya, KateRasheed

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: increased abundance in Patients with Colorectal Cancer stage I (C1)

NCBI	Quality Control	Links
Eggerthella
Gemella
Oscillibacter
Parvimonas
Peptostreptococcus
Fusobacteriota

Revision editor(s): Nithya, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/10

Curator: Nithya

Revision editor(s): Nithya

Source: Figure 2C and 4

Description: Boxplot analysis of key differential genera from diagnosis model

Abundance in Group 1: decreased abundance in Patients with Colorectal Cancer stage I (C1)

NCBI	Quality Control	Links
Corynebacterium
Ezakiella
Fenollaria
Finegoldia
Peptoniphilus
Staphylococcus
Pseudomonadota

Revision editor(s): Nithya

Experiment 6

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/10

Curator: Nithya

Revision editor(s): Nithya, Shulamite, KateRasheed

Differences from previous experiment shown

Subjects

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

Colorectal Cancer Patients (CRC)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagnosed with Colorectal Cancer (CRC)

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

261

Lab analysis

Statistical Analysis

Statistical test

Random Forest Analysis

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/10

Curator: Nithya

Revision editor(s): Nithya

Source: Figure 3A and 3B

Description: Relative abundance ratios of genera between the CRC and Polyps groups

Abundance in Group 1: decreased abundance in Colorectal Cancer Patients (CRC)

NCBI	Quality Control	Links
Corynebacterium
Ezakiella
Fenollaria
Finegoldia
Neisseria
Peptoniphilus
Staphylococcus
Varibaculum

Revision editor(s): Nithya

Experiment 7

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Healthy Volunteers (H group)

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

Colorectal Cancer patients stage IV (C4 group)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagnosed with Colorectal Cancer stage IV (C4 group)

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

120

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

15

Lab analysis

Statistical Analysis

Statistical test

ANOVA

Alpha Diversity

Richness Number of species

decreased

Signature 1

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Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, KateRasheed

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: increased abundance in Colorectal Cancer patients stage IV (C4 group)

NCBI	Quality Control	Links
Eggerthella
Parvimonas
Peptostreptococcus
Fusobacteriota

Revision editor(s): Nithya, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, KateRasheed

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: decreased abundance in Colorectal Cancer patients stage IV (C4 group)

NCBI	Quality Control	Links
Ezakiella
Fenollaria
Pseudomonadota
Staphylococcus

Revision editor(s): Nithya, KateRasheed

Experiment 8

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Patients with Polyps (P group)

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

Patients with Colorectal Cancer stage II (C2)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagonosed with Colorectal Cancer stage II (C2)

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

92

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

101

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species

decreased

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, KateRasheed

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: increased abundance in Patients with Colorectal Cancer stage II (C2)

NCBI	Quality Control	Links
Gemella
Parvimonas
Peptostreptococcus
Fusobacteriota

Revision editor(s): Nithya, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: decreased abundance in Patients with Colorectal Cancer stage II (C2)

NCBI	Quality Control	Links
Corynebacterium
Ezakiella
Fenollaria
Finegoldia
Peptoniphilus
Staphylococcus
Varibaculum
Pseudomonadota

Revision editor(s): Nithya

Experiment 9

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

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

Patients with Colorectal Cancer stage III (C3)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagonosed with Colorectal Cancer stage III (C3)

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

110

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species

unchanged

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite, KateRasheed

Source: Figure 2C and Figure 4

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: increased abundance in Patients with Colorectal Cancer stage III (C3)

NCBI	Quality Control	Links
Eggerthella
Gemella
Parvimonas
Peptostreptococcus
Fusobacteriota
Bacteroidota

Revision editor(s): Nithya, Shulamite, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite, KateRasheed

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant Phyla

Abundance in Group 1: decreased abundance in Patients with Colorectal Cancer stage III (C3)

NCBI	Quality Control	Links
Corynebacterium
Ezakiella
Fenollaria
Finegoldia
Peptoniphilus
Pseudomonadota
Staphylococcus
Varibaculum

Revision editor(s): Nithya, Shulamite, KateRasheed

Experiment 10

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, Shulamite

Differences from previous experiment shown

Subjects

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

Patients with Colorectal Cancer stage IV (C4)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients diagonosed with Colorectal Cancer stage IV (C4)

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

15

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species

decreased

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya, KateRasheed

Source: Figure 4 and 2C

Description: Boxplot analysis of key differential genera from diagnosis model and dominant phyla

Abundance in Group 1: increased abundance in Patients with Colorectal Cancer stage IV (C4)

NCBI	Quality Control	Links
Eggerthella
Parvimonas
Peptostreptococcus
Fusobacteriota

Revision editor(s): Nithya, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-4-24

Curated date: 2025/04/11

Curator: Nithya

Revision editor(s): Nithya

Source: Figure 4

Description: Boxplot analysis of key differential genera from diagnosis model

Abundance in Group 1: decreased abundance in Patients with Colorectal Cancer stage IV (C4)

NCBI	Quality Control	Links
Fenollaria
Staphylococcus
Ezakiella
Finegoldia

Revision editor(s): Nithya