Dataset Information

Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer.

ABSTRACT: Bacterial colonisation of the gut is involved in the development of colitis-associated colorectal cancer. However, it remains unclear how the gut microbiota dynamically shifts correlating with colorectal carcinogenesis. Here, we reveal the longitudinal shifts in the microbial community that occur with colitis-associated colorectal cancer. High-throughput sequencing results for the bacterial 16S rRNA gene (V3 region) were compared for azoxymethane/dextran sodium sulphate-treated mice and control mice. We found that microbial community structure was significantly altered by chronic colitis. Microbes in the species Streptococcus luteciae, Lactobacillus hamster, Bacteroides uniformis and Bacteroides ovatus were increased during colorectal carcinogenesis. Histological measurements for a molecular network including six interconnected key factors from inflammation to cancer, namely p65, p53, COX-2, PPAR?, CCR2 and ?-catenin, indicated that the microbiome modifications were correlated with molecular pathogenesis of colitis-associated colorectal cancer. Phylotype modifications after each AOM/DSS cycle were identified. A longitudinal microbial network was then constructed for the gut microbiome and showed that the phylotype shifts during this process were complex and highly dynamic. This work may provide a deeper understanding of the role of the microbiota and microbe-host interactions in colitis-associated colorectal cancer.

SUBMITTER: Liang X

PROVIDER: S-EPMC4021569 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer.

Liang Xujun X Li Huiying H Tian Geng G Li Shao S

Scientific reports 20140515

Bacterial colonisation of the gut is involved in the development of colitis-associated colorectal cancer. However, it remains unclear how the gut microbiota dynamically shifts correlating with colorectal carcinogenesis. Here, we reveal the longitudinal shifts in the microbial community that occur with colitis-associated colorectal cancer. High-throughput sequencing results for the bacterial 16S rRNA gene (V3 region) were compared for azoxymethane/dextran sodium sulphate-treated mice and control ...[more]

PMID: 24828543

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Project description:Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on bacterial growth and virulence gene expression. Given the evolving recognition of the roles for bacteria in CRC, in this work, we investigate the effects of aspirin with a focus on one oncomicrobe-Fusobacterium nucleatum We show that aspirin and its primary metabolite salicylic acid alter F. nucleatum strain Fn7-1 growth in culture and that aspirin can effectively kill both actively growing and stationary Fn7-1. We also demonstrate that, at levels that do not inhibit growth, aspirin influences Fn7-1 gene expression. To assess whether aspirin modulation of F. nucleatum may be relevant in vivo, we use the ApcMin/+ mouse intestinal tumor model in which Fn7-1 is orally inoculated daily to reveal that aspirin-supplemented chow is sufficient to inhibit F. nucleatum-potentiated colonic tumorigenesis. We expand our characterization of aspirin sensitivity across other F. nucleatum strains, including those isolated from human CRC tissues, as well as other CRC-associated microbes, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli Finally, we determine that individuals who use aspirin daily have lower fusobacterial abundance in colon adenoma tissues, as determined by quantitative PCR performed on adenoma DNA. Together, our data support that aspirin has direct antibiotic activity against F. nucleatum strains and suggest that consideration of the potential effects of aspirin on the microbiome holds promise in optimizing risk-benefit assessments for use of aspirin in CRC prevention and management.IMPORTANCE There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches. Here, we demonstrate that aspirin, an established CRC chemopreventive, exhibits specific effects on the CRC-associated Fusobacterium nucleatum in culture, an animal model of intestinal tumorigenesis, and in human colonic adenoma tissues. Our work proposes a potential role for aspirin in influencing CRC-associated bacteria to prevent colorectal adenomas and cancer, beyond aspirin's canonical anti-inflammatory role targeting host tissues. Future research, such as studies investigating the effects of aspirin on fusobacterial load in patients, will help further elucidate the prospect of using aspirin to modulate F. nucleatumin vivo for improving CRC outcomes.

Dataset Information

Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer.

Publications

Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer.

Similar Datasets

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