In search of general theories

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

26.05.2014 12:14
SCIENTIFIC REPORTS | ARTICLE OPEN
 
 
Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer
 
Xujun Liang, Huiying Li, Geng Tian & Shao Li
AffiliationsContributionsCorresponding author
Scientific Reports 4, Article number: 4985 doi:10.1038/srep04985
Received 13 January 2014 Accepted 28 April 2014 Published 15 May 2014
 
 
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, PPARγ, CCR2 and β-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.