Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Bai X, Wei H, Liu W, Coker OO, Gou H, Liu C, Zhao L, Li C, Zhou Y, Wang G, Kang W, Ng EK, Yu J
Journal
Gut
Year
2022
Keywords:
BACTERIAL PATHOGENESIS, BILE ACID METABOLISM, COLORECTAL CANCER
OBJECTIVE: Cigarette smoking is a major risk factor for colorectal cancer (CRC). We aimed to investigate whether cigarette smoke promotes CRC by altering the gut microbiota and related metabolites. DESIGN: Azoxymethane-treated C57BL/6 mice were exposed to cigarette smoke or clean air 2 hours per day for 28 weeks. Shotgun metagenomic sequencing and liquid chromatography mass spectrometry were parallelly performed on mice stools to investigate alterations in microbiota and metabolites. Germ-free mice were transplanted with stools from smoke-exposed and smoke-free control mice. RESULTS: Mice exposed to cigarette smoke had significantly increased tumour incidence and cellular proliferation compared with smoke-free control mice. Gut microbial dysbiosis was observed in smoke-exposed mice with significant differential abundance of bacterial species including the enrichment of Eggerthella lenta and depletion of Parabacteroides distasonis and Lactobacillus spp. Metabolomic analysis showed increased bile acid metabolites, especially taurodeoxycholic acid (TDCA) in the colon of smoke-exposed mice. We found that E. lenta had the most positive correlation with TDCA in smoke-exposed mice. Moreover, smoke-exposed mice manifested enhanced oncogenic MAPK/ERK (mitogen-activated protein kinase/extracellular signal‑regulated protein kinase 1/2) signalling (a downstream target of TDCA) and impaired gut barrier function. Furthermore, germ-free mice transplanted with stools from smoke-exposed mice (GF-AOMS) had increased colonocyte proliferation. Similarly, GF-AOMS showed increased abundances of gut E. lenta and TDCA, activated MAPK/ERK pathway and impaired gut barrier in colonic epithelium. CONCLUSION: The gut microbiota dysbiosis induced by cigarette smoke plays a protumourigenic role in CRC. The smoke-induced gut microbiota dysbiosis altered gut metabolites and impaired gut barrier function, which could activate oncogenic MAPK/ERK signalling in colonic epithelium.

Experiment 2


Needs review

Curated date: 2023/03/07

Curator: Busayo

Revision editor(s): Busayo, Mcarlson, Dupe

Differences from previous experiment shown

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled (if applicable)
Mus musculus
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
Smoke free group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Smoke-exposed
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice exposed to cigarette smoke directly (4% of 2000 mL/ min airflow) 2 hours per day for 28 weeks.
Group 0 sample size Number of subjects in the control (unexposed) group
15
Group 1 sample size Number of subjects in the case (exposed) group
15

Lab analysis

Sequencing type
WMS
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
PERMANOVA
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

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2023/03/08

Curator: Busayo

Revision editor(s): Busayo, Mcarlson

Source: Figure 2c

Description: Differentially abundant bacteria in smoke-free and smoke-exposed mice intraperitoneally injected with carcinogen azoxymethane

Abundance in Group 1: increased abundance in Smoke-exposed

NCBI Quality ControlLinks
Bacillus thuringiensis
Bacillus velezensis
Bifidobacterium choerinum
Eggerthella lenta
Escherichia coli
Gordonibacter massiliensis (ex Traore et al. 2017)
Gordonibacter pamelaeae
Gordonibacter urolithinfaciens
Muribaculum gordoncarteri
Staphylococcus capitis
Parolsenella massiliensis

Revision editor(s): Busayo, Mcarlson

Signature 2

Needs review

Curated date: 2023/03/08

Curator: Busayo

Revision editor(s): Busayo, Mcarlson

Source: Figure 2c

Description: Differentially abundant bacteria in smoke-free and smoke-exposed mice intraperitoneally injected with carcinogen azoxymethane

Abundance in Group 1: decreased abundance in Smoke-exposed

NCBI Quality ControlLinks
Bacteroides cellulosilyticus
Clostridiales bacterium CCNA10
Erysipelotrichaceae bacterium GAM147
Limosilactobacillus reuteri
Parabacteroides distasonis
Parabacteroides sp. CT06
Phocaeicola dorei
Phocaeicola vulgatus
Streptococcus suis

Revision editor(s): Busayo, Mcarlson