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

Study information

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

35387878

DOI Digital object identifier for electronic documents.

http://dx.doi.org/10.1136/gutjnl-2021-325021

URI

https://gut.bmj.com/content/71/12/2439

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

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/03/07

Curator: Busayo

Revision editor(s): Mcarlson, Busayo, Dupe, Peace Sandy, ChiomaBlessing

Differences from previous experiment shown

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: 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,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Smoking behavior smoking,Smoking behavior,smoking behavior

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Smoke-free control group intraperitoneally injected with carcinogen azoxymethane (AOM) (10 mg/kg)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Smoke-exposed group intraperitoneally injected with carcinogen, AOM (AOM + Smoking)

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 (at end time point)

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

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).: arcsine square-root

Statistical test: MaAsLin2

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

Signature 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/03/08

Curator: Busayo

Revision editor(s): Busayo, Mcarlson, ChiomaBlessing

Source: Figure 2c

Description: Differentially abundant bacteria in smoke-free and smoke-exposed mice (AOM vs AOM + Smoking)

Abundance in Group 1: increased abundance in Smoke-exposed group intraperitoneally injected with carcinogen, AOM (AOM + Smoking)

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

Revision editor(s): Busayo, Mcarlson, ChiomaBlessing

Signature 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/03/08

Curator: Busayo

Revision editor(s): Busayo, Mcarlson, ChiomaBlessing

Source: Figure 2c

Description: Differentially abundant bacteria in smoke-free and smoke-exposed mice (AOM vs AOM + Smoking)

Abundance in Group 1: decreased abundance in Smoke-exposed group intraperitoneally injected with carcinogen, AOM (AOM + Smoking)

NCBI	Quality Control	Links
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, ChiomaBlessing