Human oral microbiome dysbiosis as a novel non-invasive biomarker in detection of colorectal cancer

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Zhang S, Kong C, Yang Y, Cai S, Li X, Cai G, Ma Y
Journal
Theranostics
Year
2020
Keywords:
16S rRNA, colorectal adenomas, colorectal cancers, oral microbiome
Background: The oral microbiome may play an important role in colorectal carcinogenesis. However, few studies have investigated the association between oral microbiome and the development of colorectal cancer (CRC). We aimed to investigate whether oral health-colorectal tumor association has an underlying microbial basis, in the quest for novel non-invasive biomarkers for CRC. Methods: We collected oral swab samples from 161 patients with CRC, 34 patients with colorectal adenoma (CRA), and 58 healthy volunteers. The oral microbiota was assessed using 16S rRNA sequencing. We characterized oral microbiome, identified microbial markers, constructed and validated colorectal tumor (CRA and CRC) classifier. Results: Oral microbial composition and diversity were significantly different among the three groups, and the CRA group had the highest diversity. Analysis of the functional potential of oral microbiota demonstrated that the pathway involving cell motility was overrepresented in the CRA and CRC groups relative to that in the healthy controls. Moreover, a random forest model was constructed based on oral microbial markers, which could distinguish the colorectal tumor groups from the healthy controls and achieve a powerful classification potential in the discovery and validation cohorts. Conclusion: This study suggests a potential association between oral microbiome dysbiosis and colorectal cancer. Oral microbiota-based biomarkers may be helpful in predicting the risks for the development of CRA and CRC.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/6

Curated date: 2022/06/19

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1, WikiWorks

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
Oral cavity Bucca,Buccal cavity,Cavity of mouth,Oral cavity,oral cavity
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 Individuals
Group 1 name Corresponds to the case (exposed) group for case-control studies
CRC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with colorectal cancer
Group 0 sample size Number of subjects in the control (unexposed) group
58
Group 1 sample size Number of subjects in the case (exposed) group
161

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Welch's T-Test
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, smoking status, alcohol drinking

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/22

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S9 / Figure S1F

Description: Differential microbial abundance between CRC cohort and controls

Abundance in Group 1: increased abundance in CRC

NCBI Quality ControlLinks
Anaerococcus
Anaerostipes
Brachybacterium
Bradyrhizobium
Cloacibacterium
Cyanobacteriota
Gemella
Micrococcus
Neisseria
Pantoea
Pseudomonas
Psychrobacter
Spartobacteria
Streptococcus
Thermoflavimicrobium

Revision editor(s): Jeshudy, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/22

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S9

Description: Differential microbial abundance between CRC cohort and controls

Abundance in Group 1: decreased abundance in CRC

NCBI Quality ControlLinks
unclassified Bacteroidota
Fusobacteriota
Actinomycetota
Candidatus Saccharibacteria
Spirochaetota
Synergistota
Cyanobacteriota
Veillonella
Actinomyces
Prevotella
Fusobacterium
Lysobacter

Revision editor(s): Jeshudy, Claregrieve1

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/19

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Colorectal adenoma adenoma of large bowel,adenoma of large intestine,adenoma of the large bowel,adenoma of the large intestine,colorectal adenoma,colorectum adenoma,large bowel adenoma,large intestine adenoma,Colorectal adenoma
Group 1 name Corresponds to the case (exposed) group for case-control studies
CRA
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with colorectal adenoma
Group 1 sample size Number of subjects in the case (exposed) group
34

Lab analysis

Statistical Analysis

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/22

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S6-7

Description: Differential microbial abundance between CRA cohort and controls

Abundance in Group 1: increased abundance in CRA

NCBI Quality ControlLinks
Bacillota
Acidobacteriota
Gemmatimonadia
Nitrospira
Chloroflexota
Verrucomicrobiota
Streptococcus
Cyanobacteriota incertae sedis
Gemella
Gemmatimonas
Gemmiger
Spartobacteria
Bradyrhizobium
Brachybacterium
unclassified Intrasporangiaceae
Xanthomonas

Revision editor(s): Jeshudy, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/22

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S6-7

Description: Differential microbial abundance between CRA cohort and controls

Abundance in Group 1: decreased abundance in CRA

NCBI Quality ControlLinks
Actinomyces
Aestuariicoccus
Aggregatibacter
Alloprevotella
Anaeroglobus
Anaerovorax
Anoxybacillus
Asteroleplasma
Atopobium
Butyrivibrio
Campylobacter
Candidatus Saccharibacteria
Capnocytophaga
Corynebacterium
Dialister
Diaphorobacter
Eggerthia
Eubacterium
Bacillota
Fretibacterium
Fusobacterium
Lachnoanaerobaculum
Leptotrichia
Lysobacter
Mycoplasma
Neisseria
Oribacterium
Parvimonas
Peptococcus
Peptostreptococcaceae incertae sedis
Peptostreptococcus
Phyllobacterium
Porphyromonas
Prevotella
Propionibacteriaceae
Propionibacterium
Solobacterium
Stomatobaculum
Streptophyta
Tannerella
Treponema
Veillonella
Xanthomonas
Candidatus Saccharibacteria incertae sedis
Campylobacter sp.
unclassified Bacteroidota
Fusobacteriota
Cyanobacteriota
Spirochaetota
Actinomycetota
Synergistota
Mycoplasmatota
Pseudomonadota

Revision editor(s): Jeshudy, Claregrieve1

Experiment 3


Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/22

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1, WikiWorks

Differences from previous experiment shown

Subjects

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
CRA
Group 1 name Corresponds to the case (exposed) group for case-control studies
CRC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with colorectal cancer
Group 0 sample size Number of subjects in the control (unexposed) group
34
Group 1 sample size Number of subjects in the case (exposed) group
161

Lab analysis

Statistical Analysis

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/22

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S4-5

Description: Differential microbial abundance between CRC and CRA groups

Abundance in Group 1: decreased abundance in CRC

NCBI Quality ControlLinks
unclassified Bacteroidota
Candidatus Saccharibacteria
Pseudomonadota
Fusobacteriota
Porphyromonas
Diaphorobacter
Neisseria
Prevotella
Phyllobacterium
Comamonas
Solobacterium
Anaerococcus
Capnocytophaga
Peptostreptococcus
Fusobacterium
Aggregatibacter
Brachymonas
Candidatus Saccharibacteria incertae sedis
unclassified Alphaproteobacteria
Parvimonas
Cloacibacterium
Campylobacter
Eubacterium
Formosa

Revision editor(s): Jeshudy, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/7

Curated date: 2022/06/22

Curator: Jeshudy

Revision editor(s): Jeshudy, Claregrieve1

Source: Table S4-5

Description: Differential microbial abundance between CRC and CRA groups

Abundance in Group 1: increased abundance in CRC

NCBI Quality ControlLinks
Blautia
Cyanobacteriota
Gemmatimonas
Gemmiger
Megamonas
Streptococcus
Streptophyta
Xanthomonas
unclassified Oscillospiraceae
Bacillota
Acidobacteriota
Chloroflexota
Gemmatimonadales

Revision editor(s): Jeshudy, Claregrieve1