Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations

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
Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ
Journal
PloS one
Year
2016
BACKGROUND AND AIMS: Investigation of microbe-metabolite relationships in the gut is needed to understand and potentially reduce colorectal cancer (CRC) risk. METHODS: Microbiota and metabolomics profiling were performed on lyophilized feces from 42 CRC cases and 89 matched controls. Multivariable logistic regression was used to identify statistically independent associations with CRC. First principal coordinate-component pair (PCo1-PC1) and false discovery rate (0.05)-corrected P-values were calculated for 116,000 Pearson correlations between 530 metabolites and 220 microbes in a sex*case/control meta-analysis. RESULTS: Overall microbe-metabolite PCo1-PC1 was more strongly correlated in cases than in controls (Rho 0.606 vs 0.201, P = 0.01). CRC was independently associated with lower levels of Clostridia, Lachnospiraceae, p-aminobenzoate and conjugated linoleate, and with higher levels of Fusobacterium, Porphyromonas, p-hydroxy-benzaldehyde, and palmitoyl-sphingomyelin. Through postulated effects on cell shedding (palmitoyl-sphingomyelin), inflammation (conjugated linoleate), and innate immunity (p-aminobenzoate), metabolites mediated the CRC association with Fusobacterium and Porphyromonas by 29% and 34%, respectively. Overall, palmitoyl-sphingomyelin correlated directly with abundances of Enterobacteriaceae (Gammaproteobacteria), three Actinobacteria and five Firmicutes. Only Parabacteroides correlated inversely with palmitoyl-sphingomyelin. Other lipids correlated inversely with Alcaligenaceae (Betaproteobacteria). Six Bonferroni-significant correlations were found, including low indolepropionate and threnoylvaline with Actinobacteria and high erythronate and an uncharacterized metabolite with Enterobacteriaceae. CONCLUSIONS: Feces from CRC cases had very strong microbe-metabolite correlations that were predominated by Enterobacteriaceae and Actinobacteria. Metabolites mediated a direct CRC association with Fusobacterium and Porphyromonas, but not an inverse association with Clostridia and Lachnospiraceae. This study identifies complex microbe-metabolite networks that may provide insights on neoplasia and targets for intervention.

Experiment 1


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

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 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
controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
adenocarcinoma of colon and rectum patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Not stated
Group 0 sample size Number of subjects in the control (unexposed) group
89
Group 1 sample size Number of subjects in the case (exposed) group
42

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
Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Logistic Regression
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
Matched on Factors on which subjects have been matched on in a case-control study
body mass index, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex


Signature 1

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

Curated date: 2021/01/10

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks

Source: Table 2

Description: Fecal microbes independently associated with colorectal cancer

Abundance in Group 1: increased abundance in adenocarcinoma of colon and rectum patients

NCBI Quality ControlLinks
Fusobacterium
Porphyromonas

Revision editor(s): WikiWorks

Signature 2

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

Curated date: 2021/01/10

Curator: Nidhi Saini

Revision editor(s): WikiWorks

Source: Table 2

Description: Fecal microbes independently associated with colorectal cancer

Abundance in Group 1: decreased abundance in adenocarcinoma of colon and rectum patients

NCBI Quality ControlLinks
Clostridia
Lachnospiraceae

Revision editor(s): WikiWorks