Potential of fecal microbiota for early-stage detection of colorectal cancer

From BugSigDB
Reviewed Marked as Reviewed by Fatima on 2023-3-7
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Zeller G, Tap J, Voigt AY, Sunagawa S, Kultima JR, Costea PI, Amiot A, Böhm J, Brunetti F, Habermann N, Hercog R, Koch M, Luciani A, Mende DR, Schneider MA, Schrotz-King P, Tournigand C, Tran Van Nhieu J, Yamada T, Zimmermann J, Benes V, Kloor M, Ulrich CM, von Knebel Doeberitz M, Sobhani I, Bork P
Journal
Molecular systems biology
Year
2014
Keywords:
cancer screening, colorectal cancer, fecal biomarkers, human gut microbiome, metagenomics
Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.

Experiment 1


Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2022/01/10

Curator: Itslanapark

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

Subjects

Location of subjects
France
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 cancer of large bowel,cancer of large intestine,cancer of the large bowel,cancer of the large intestine,carcinoma of colorectum,carcinoma of large bowel,carcinoma of large intestine,carcinoma of the large bowel,carcinoma of the large intestine,colorectal (colon or rectal) cancer,colorectal cancer,colorectal carcinoma,colorectum carcinoma,CRC,large bowel cancer,large bowel carcinoma,large intestine cancer,large intestine carcinoma,Colorectal carcinoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Neoplasia-free
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 referred for colonoscopy that had cancerous tumors
Group 0 sample size Number of subjects in the control (unexposed) group
61
Group 1 sample size Number of subjects in the case (exposed) group
53
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
none

Lab analysis

Sequencing type
WMS
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

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)
.1
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
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2022/01/19

Curator: Itslanapark

Revision editor(s): Itslanapark, Fatima

Source: Supplementary Figure S2

Description: significant differences in the abundance of specific taxa

Abundance in Group 1: increased abundance in CRC patients

NCBI Quality ControlLinks
Bacteroides
Bilophila
Desulfovibrio
Fusobacteriota
Fusobacterium
Fusobacterium animalis
Fusobacterium nucleatum subsp. nucleatum
Fusobacterium polymorphum
Fusobacterium vincentii
Leptotrichia
Parvimonas
Peptostreptococcus
Porphyromonas
Porphyromonas asaccharolytica
Prevotella nigrescens
Pseudoflavonifractor
Pseudoflavonifractor capillosus
Pseudomonadota
Selenomonas
uncultured Oscillospiraceae bacterium
Peptostreptococcus stomatis
Leptotrichia hofstadii
unclassified Parvimonas
Fusobacterium periodonticum
Parvimonas micra
Bacteroides fragilis
Bilophila wadsworthia
unclassified Neisseria
Campylobacter rectus
Selenomonas sputigena
Leptotrichia buccalis
[Clostridium] hylemonae
[Clostridium] symbiosum

Revision editor(s): Itslanapark, Fatima

Signature 2

Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2022/01/19

Curator: Itslanapark

Revision editor(s): Itslanapark, Fatima

Source: Supplementary Figure S2

Description: significant differences in the abundance of specific taxa

Abundance in Group 1: decreased abundance in CRC patients

NCBI Quality ControlLinks
Acinetobacter
Anaerobutyricum hallii
Bacillota
Campylobacter
Eubacterium
Eubacterium ventriosum
Lachnospira eligens
Roseburia intestinalis
Ruminococcus
Ruminococcus bromii
Streptococcus salivarius
unclassified Ruminococcus
Agathobacter rectalis

Revision editor(s): Itslanapark, Fatima

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): Fatima, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Colorectal carcinoma cancer of large bowel,cancer of large intestine,cancer of the large bowel,cancer of the large intestine,carcinoma of colorectum,carcinoma of large bowel,carcinoma of large intestine,carcinoma of the large bowel,carcinoma of the large intestine,colorectal (colon or rectal) cancer,colorectal cancer,colorectal carcinoma,colorectum carcinoma,CRC,large bowel cancer,large bowel carcinoma,large intestine cancer,large intestine carcinoma,Colorectal carcinoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Adenoma patients
Group 0 sample size Number of subjects in the control (unexposed) group
42

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): Fatima

Source: Supplementary Figure S2

Description: significant differences in the abundance of specific taxa between CRC and Adenoma patients

Abundance in Group 1: increased abundance in CRC patients

NCBI Quality ControlLinks
Fusobacteriia
Fusobacterium
Fusobacterium animalis
Fusobacterium nucleatum subsp. nucleatum
Fusobacterium polymorphum
Fusobacterium vincentii
Olsenella
Parvimonas
Peptostreptococcus
Porphyromonas
Porphyromonas asaccharolytica
Pseudomonadota
Prevotella nigrescens
Peptostreptococcus stomatis
unclassified Parvimonas
Parvimonas micra
Olsenella uli
Streptococcus anginosus

Revision editor(s): Fatima

Signature 2

Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): Fatima

Source: Supplementary Figure S2

Description: significant differences in the abundance of specific taxa between CRC and Adenoma patients

Abundance in Group 1: decreased abundance in CRC patients

NCBI Quality ControlLinks
Agathobacter rectalis
Eubacterium

Revision editor(s): Fatima

Experiment 3


Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): WikiWorks, Lwaldron, Fatima, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Neoplasia free
Group 1 name Corresponds to the case (exposed) group for case-control studies
Adenoma patients
Group 0 sample size Number of subjects in the control (unexposed) group
61
Group 1 sample size Number of subjects in the case (exposed) group
42

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): Fatima

Source: Supplementary Figure S2

Description: significant differences in the abundance of specific taxa between Adenoma patients and neoplasia free

Abundance in Group 1: decreased abundance in Adenoma patients

NCBI Quality ControlLinks
Ruminococcus

Revision editor(s): Fatima

Experiment 4


Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): Fatima, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Neoplasia free control
Group 1 name Corresponds to the case (exposed) group for case-control studies
CRC
Group 0 sample size Number of subjects in the control (unexposed) group
88
Group 1 sample size Number of subjects in the case (exposed) group
53

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): Fatima

Source: Supplementary Figure S3

Description: Microbial taxa significantly different between CRC patients to the control group (consisting of neoplasia-free and ones with small adenomas)

Abundance in Group 1: increased abundance in CRC

NCBI Quality ControlLinks
Fusobacteriia
Pseudomonadota
Desulfovibrio
Fusobacterium
Parvimonas
Peptostreptococcus
Pseudoflavonifractor
Porphyromonas
Campylobacter
Fusobacterium animalis
Peptostreptococcus stomatis
Bacteroides fragilis
[Clostridium] symbiosum
Parvimonas micra
Fusobacterium vincentii
Bilophila wadsworthia
Pseudoflavonifractor capillosus
Hungatella hathewayi CAG:224
unclassified Parvimonas
Fusobacterium periodonticum
Fusobacterium gonidiaformans
Segatella oris
Prevotella nigrescens
Porphyromonas asaccharolytica

Revision editor(s): Fatima

Signature 2

Reviewed Marked as Reviewed by Fatima on 2023-3-7

Curated date: 2023/03/07

Curator: Fatima

Revision editor(s): Fatima

Source: Supplementary Figure S3

Description: Microbial taxa significantly different between CRC patients to the control group (consisting of neoplasia-free and ones with small adenomas)

Abundance in Group 1: decreased abundance in CRC

NCBI Quality ControlLinks
Bacillota
Bilophila
Methanosphaera
Ruminococcus
Eubacterium
Methanosphaera stadtmanae
unclassified Ruminococcus
Streptococcus salivarius
Anaerobutyricum hallii
Lachnospira eligens
Agathobacter rectalis
Roseburia intestinalis
Eubacterium ventriosum

Revision editor(s): Fatima