Integrated microbiome and metabolome analysis reveals a novel interplay between commensal bacteria and metabolites in colorectal cancer

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Yang Y, Misra BB, Liang L, Bi D, Weng W, Wu W, Cai S, Qin H, Goel A, Li X, Ma Y
Journal
Theranostics
Year
2019
Keywords:
biomarkers, colorectal cancer, gut, metabolomics, microbiome
Rationale: Colorectal cancer (CRC) is a malignant tumor with the third highest morbidity rate among all cancers. Driven by the host's genetic makeup and environmental exposures, the gut microbiome and its metabolites have been implicated as the causes and regulators of CRC pathogenesis. We assessed human fecal samples as noninvasive and unbiased surrogates to catalog the gut microbiota and metabolome in patients with CRC. Methods: Fecal samples collected from CRC patients (CRC group, n = 50) and healthy volunteers (H group, n = 50) were subjected to microbiome (16S rRNA gene sequencing) and metabolome (gas chromatography-mass spectrometry, GC-MS) analyses. The datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches. Results: Fecal metabolomic analysis led to the identification of 164 metabolites spread across 40 metabolic pathways in both groups. In addition, there were 42 and 17 metabolites specific to the H and CRC groups, respectively. Sequencing of microbial diversity revealed 1084 operational taxonomic units (OTUs) across the two groups, and there was less species diversity in the CRC group than in the H group. Seventy-six discriminatory OTUs were identified for the microbiota of H volunteers and CRC patients. Integrated analysis correlated CRC-associated microbes with metabolites, such as polyamines (cadaverine and putrescine). Conclusions: Our results provide substantial evidence of a novel interplay between the gut microbiome and metabolome (i.e., polyamines), which is drastically perturbed in CRC. Microbe-associated metabolites can be used as diagnostic biomarkers in therapeutic explorations.

Experiment 1


Needs review

Curated date: 2022/01/28

Curator: Itslanapark

Revision editor(s): Itslanapark, WikiWorks, Atrayees

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled (if applicable)
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
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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls
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 diagnosed with colorectal cancer
Group 0 sample size Number of subjects in the control (unexposed) group
50
Group 1 sample size Number of subjects in the case (exposed) group
50
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 months

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
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
.05
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4
Matched on Factors on which subjects have been matched on in a case-control study
age, sex, body mass index, education level, smoking behavior, Matched on: "tumor location" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.tumor location, Matched on: "tumor size" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.tumor size, hypertension, hypertension, Matched on: "appendectomy" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.appendectomy

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2022/02/20

Curator: Itslanapark

Revision editor(s): Itslanapark, Aiyshaaaa

Source: Figure 2(b)

Description: The differences in abundance between the H and CRC groups.

Abundance in Group 1: increased abundance in CRC patients

NCBI Quality ControlLinks
Escherichia/Shigella sp.
Fusobacteriota
Fusobacterium
Lentisphaera
Parvimonas
Porphyromonas
Pseudomonadota
Akkermansia
Pseudomonadales
Fusobacteriaceae
Fusobacteriia
Fusobacteriales
Enterobacteriaceae

Revision editor(s): Itslanapark, Aiyshaaaa

Signature 2

Needs review

Curated date: 2022/02/20

Curator: Itslanapark

Revision editor(s): Itslanapark, Aiyshaaaa

Source: Figure 2(b)

Description: The differences in abundance between the H and CRC groups.

Abundance in Group 1: decreased abundance in CRC patients

NCBI Quality ControlLinks
Acidaminococcaceae
Actinomycetota
Bacillota
Blautia
Clostridia
Eubacteriales
Eubacterium coprostanoligenes
Eubacterium oxidoreducens
Faecalibacterium
Lachnospira
Lachnospiraceae
Megamonas
Negativicutes
Oscillospiraceae
Phascolarctobacterium
Pseudobutyrivibrio
Selenomonadales
Romboutsia
Solibacillus
Parasutterella
Bifidobacteriaceae
Bifidobacterium
Bifidobacteriales
Subdoligranulum

Revision editor(s): Itslanapark, Aiyshaaaa