The gut microbiota in conventional and serrated precursors of colorectal cancer

From BugSigDB
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Peters BA, Dominianni C, Shapiro JA, Church TR, Wu J, Miller G, Yuen E, Freiman H, Lustbader I, Salik J, Friedlander C, Hayes RB, Ahn J
Journal
Microbiome
Year
2016
Keywords:
Adenoma, Cancer, Colorectal, Microbiome, Microbiota, Polyp, Serrated
BACKGROUND: Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types. RESULTS: Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases (n = 144), serrated polyp cases (n = 73), or polyp-free controls (n = 323). CA cases were further classified as proximal (n = 87) or distal (n = 55) and as non-advanced (n = 121) or advanced (n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups. CA cases had lower species richness in stool than controls (p = 0.03); in particular, this association was strongest for advanced CA cases (p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls (p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases. CONCLUSIONS: Our results indicate that gut microbes may play a role in the early stages of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.

Experiment 1


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks, ChiomaBlessing

Subjects

Location of subjects
United States of America
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 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 0 name Corresponds to the control (unexposed) group for case-control studies
controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
conventional adenoma cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
conventional adenoma cases; those with at least one tubular or tubulovillous adenoma and no other polyps of hyperplastic, SSA, or unclassified histology. HP cases; having at least one HP, with no other polyps of tubular, tubulovillous, SSA, or unclassified histology. SSA cases; having at least one SSA, with or without HP(s), and with no other polyps of tubular, tubulovillous, or unclassified histology. Proximal polyps; polyps located in the cecum, ascending colon, hepatic flexure, transverse colon, or splenic flexure. Distal polyps; polyps located in the descending colon, sigmoid colon, or rectum.
Group 0 sample size Number of subjects in the control (unexposed) group
323
Group 1 sample size Number of subjects in the case (exposed) group
144
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
NYU included who had not been on long-term antibiotic treatment

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
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).
raw counts
Statistical test
DESeq2
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
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
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Fatima on 2021/06/29

Curated date: 2021/01/10

Curator: Levi Waldron

Revision editor(s): WikiWorks

Source: Table 2 + Supplemental Table S5 + S3+ S4

Description: Differential abundance was detected by the “DESeq” function in the DESeq2 package. All classes and genera with an FDR-adjusted q < 0.10 are included in the table. Models were adjusted for sex, age, study, and categorical BMI. See Additional file 1: Table S5 for comparisons at the phylum, order, and family level

Abundance in Group 1: increased abundance in conventional adenoma cases

NCBI Quality ControlLinks
Bacilli
Gammaproteobacteria
Actinomyces
Corynebacterium
Streptococcus
Peptoniphilus
Dorea
Phascolarctobacterium
Sutterella
Actinomycetales
Actinomycetaceae
Alcaligenaceae
Lactobacillales
Streptococcaceae
Veillonellaceae
Enterobacterales
Corynebacteriaceae
Lacticaseibacillus zeae
Bacillus
Bacillaceae

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Levi Waldron

Revision editor(s): WikiWorks

Source: Table 2 + Supplemental Table S5 + S3+ S4

Description: Differential abundance was detected by the “DESeq” function in the DESeq2 package. All classes and genera with an FDR-adjusted q < 0.10 are included in the table. Models were adjusted for sex, age, study, and categorical BMI. See Additional file 1: Table S5 for comparisons at the phylum, order, and family level

Abundance in Group 1: decreased abundance in conventional adenoma cases

NCBI Quality ControlLinks
Coprobacillus
Cyanobacteriota

Revision editor(s): WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Hyperplastic Polyp Hp,hyperplastic polyp,metaplastic polyp,MP,Hyperplastic Polyp,hyperplastic Polyp
Group 1 name Corresponds to the case (exposed) group for case-control studies
hyperplastic polyp cases
Group 1 sample size Number of subjects in the case (exposed) group
40

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 Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Levi Waldron

Revision editor(s): WikiWorks

Source: Table 2 + Supplemental Table S5 + S3+ S4

Description: Differential abundance was detected by the “DESeq” function in the DESeq2 package. All classes and genera with an FDR-adjusted q < 0.10 are included in the table. Models were adjusted for sex, age, study, and categorical BMI. See Additional file 1: Table S5 for comparisons at the phylum, order, and family level

Abundance in Group 1: increased abundance in hyperplastic polyp cases

NCBI Quality ControlLinks
Anaerostipes
Lacticaseibacillus zeae

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Levi Waldron

Revision editor(s): WikiWorks

Source: Table 2 + Supplemental Table S5 + S3+ S4

Description: Differential abundance was detected by the “DESeq” function in the DESeq2 package. All classes and genera with an FDR-adjusted q < 0.10 are included in the table. Models were adjusted for sex, age, study, and categorical BMI. See Additional file 1: Table S5 for comparisons at the phylum, order, and family level

Abundance in Group 1: decreased abundance in hyperplastic polyp cases

NCBI Quality ControlLinks
Gammaproteobacteria
Coprobacillus
Enterobacterales

Revision editor(s): WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Colon Sessile Serrated Adenoma/Polyp colon sessile serrated adenoma,colon sessile serrated adenoma/polyp,colon sessile serrated polyp,colon SSA,colon SSA/P,colon SSP,sessile serrated adenoma,Colon Sessile Serrated Adenoma/Polyp,colon Sessile Serrated Adenoma/Polyp
Group 1 name Corresponds to the case (exposed) group for case-control studies
Sessile serrated adenoma cases
Group 1 sample size Number of subjects in the case (exposed) group
33

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 Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Levi Waldron

Revision editor(s): WikiWorks

Source: Table 2 + Supplemental Table S5 + S3+ S4

Description: Differential abundance was detected by the “DESeq” function in the DESeq2 package. All classes and genera with an FDR-adjusted q < 0.10 are included in the table. Models were adjusted for sex, age, study, and categorical BMI. See Additional file 1: Table S5 for comparisons at the phylum, order, and family level

Abundance in Group 1: decreased abundance in Sessile serrated adenoma cases

NCBI Quality ControlLinks
Erysipelotrichia
Gammaproteobacteria

Revision editor(s): WikiWorks

Experiment 4


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks, ChiomaBlessing

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
Proximal conventional adenoma cases
Group 1 sample size Number of subjects in the case (exposed) group
87

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 Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Marianthi Thomatos

Revision editor(s): WikiWorks

Source: Supplemental Table S6 + S3

Description: Differentially abundant taxa (phylum‐OTU level) between controls and proximal or distal conventional adenoma cases, as detected by the DESeq function in the DESeq2 package. Models were adjusted for age, sex, categorical BMI, and study. All taxa with an FDR‐adjusted q<0.10 are included in the table.

Abundance in Group 1: increased abundance in Proximal conventional adenoma cases

NCBI Quality ControlLinks
Actinomycetales
Actinomycetaceae
Actinomyces
Corynebacteriaceae
Corynebacterium
Streptococcaceae
Clostridium
Porphyromonas
Bacilli
Lactobacillales
Peptoniphilus
Streptococcus
Tissierellaceae
Anaerococcus
Odoribacter
Veillonellaceae
Anaerostipes
Dorea
Sutterella
Phascolarctobacterium
Alcaligenaceae
Enterobacterales
Gammaproteobacteria
Odoribacteraceae

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Marianthi Thomatos

Revision editor(s): WikiWorks

Source: Supplemental Table S6 + S3

Description: Differentially abundant taxa (phylum‐OTU level) between controls and proximal or distal conventional adenoma cases, as detected by the DESeq function in the DESeq2 package. Models were adjusted for age, sex, categorical BMI, and study. All taxa with an FDR‐adjusted q<0.10 are included in the table.

Abundance in Group 1: decreased abundance in Proximal conventional adenoma cases

NCBI Quality ControlLinks
Coprobacillus

Revision editor(s): WikiWorks

Experiment 5


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Distal conventional adenoma cases
Group 1 sample size Number of subjects in the case (exposed) group
55

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 2021/06/29

Curated date: 2021/01/10

Curator: Marianthi Thomatos

Revision editor(s): WikiWorks, Lwaldron, Fatima, Merit, Davvve

Source: Supplemental Table S6 + S3

Description: Differentially abundant taxa (phylum‐OTU level) between controls and proximal or distal conventional adenoma cases, as detected by the DESeq function in the DESeq2 package. Models were adjusted for age, sex, categorical BMI, and study. All taxa with an FDR‐adjusted q<0.10, are included in the table.

Abundance in Group 1: decreased abundance in Distal conventional adenoma cases

NCBI Quality ControlLinks
Christensenellaceae
Clostridia
Clostridiaceae
Clostridium
Enterococcaceae
Enterococcus
Mollicutes
Synergistota

Revision editor(s): WikiWorks, Lwaldron, Fatima, Merit, Davvve

Experiment 6


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-advanced conventional adenoma cases
Group 1 sample size Number of subjects in the case (exposed) group
121

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 Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Marianthi Thomatos

Revision editor(s): WikiWorks

Source: Supplemental Table S6 + S3

Description: Differentially abundant taxa (phylum‐OTU level) between controls and non‐advanced or advanced conventional adenoma cases, as detected by the DESeq function in the DESeq2 package. Models were adjusted for age, sex, categorical BMI, and study. All taxa with an FDR‐adjusted q<0.10 are included in the table.

Abundance in Group 1: increased abundance in Non-advanced conventional adenoma cases

NCBI Quality ControlLinks
Actinomyces
Odoribacter
Bacilli
Lactobacillales
Lacticaseibacillus zeae
Streptococcaceae
Streptococcus
Dorea
Veillonellaceae
Sutterella
Alcaligenaceae
Phascolarctobacterium

Revision editor(s): WikiWorks

Experiment 7


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
advanced conventional adenoma cases
Group 1 sample size Number of subjects in the case (exposed) group
22

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Marianthi Thomatos

Revision editor(s): WikiWorks

Source: Supplemental Table S7 + S3

Description: Differentially abundant taxa (phylum‐OTU level) between controls and non‐advanced or advanced conventional adenoma cases, as detected by the DESeq function in the DESeq2 package. Models were adjusted for age, sex, categorical BMI, and study. All taxa with an FDR‐adjusted q<0.10 are included in the table.

Abundance in Group 1: increased abundance in advanced conventional adenoma cases

NCBI Quality ControlLinks
Actinomycetales
Actinomycetaceae
Actinomyces
Corynebacterium
Porphyromonas
Tissierellaceae
Anaerococcus
Finegoldia
Peptoniphilus
Pasteurellales
Pasteurellaceae
Haemophilus
Corynebacteriaceae

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Marianthi Thomatos

Revision editor(s): WikiWorks

Source: Supplemental Table S7 + S3

Description: Differentially abundant taxa (phylum‐OTU level) between controls and non‐advanced or advanced conventional adenoma cases, as detected by the DESeq function in the DESeq2 package. Models were adjusted for age, sex, categorical BMI, and study. All taxa with an FDR‐adjusted q<0.10 are included in the table.

Abundance in Group 1: decreased abundance in advanced conventional adenoma cases

NCBI Quality ControlLinks
Barnesiellaceae
Cyanobacteriota
Christensenellaceae
Lachnobacterium
Lachnospira
Alphaproteobacteria

Revision editor(s): WikiWorks