Oncotarget

Research Papers:

Evolutionary biologic changes of gut microbiota in an ‘adenoma-carcinoma sequence’ mouse colorectal cancer model induced by 1, 2-Dimethylhydrazine

Teng Sun, Shanglong Liu, Yanbing Zhou _, Zengwu Yao, Dongfeng Zhang, Shougen Cao, Zhiliang Wei, Bin Tan, Yi Li, Zheng Lian and Song Wang

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Oncotarget. 2017; 8:444-457. https://doi.org/10.18632/oncotarget.13443

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Abstract

Teng Sun2, Shanglong Liu1, Yanbing Zhou1, Zengwu Yao3, Dongfeng Zhang4, Shougen Cao1, Zhiliang Wei1, Bin Tan1, Yi Li1, Zheng Lian5, Song Wang6

1Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China

2Department of General Surgery, Qingdao municipal hospital, Qingdao, China

3Department of General Surgery, Yantai Yuhuangding Hospital, Yantai, China

4Department of Epidemiology and Health Statistics, Qingdao University Medical College, Qingdao, China

5Department of General Surgery, Zhucheng People’s Hospital, Weifang, China

6Department of General Surgery, Linzi District People’s Hospital, Zibo, China

Correspondence to:

Yanbing Zhou, email: zhouyanbing999@aliyun.com

Keywords: colorectal cancer, microbiology, animal model

Received: June 16, 2016     Accepted: November 12, 2016     Published: November 18, 2016

ABSTRACT

The molecular biological mechanisms underlying the evolutionary biologic changes leading to carcinogenesis remain unclear. The main objective of our study was to explore the evolution of the microbiota community and molecules related with CRC in the dynamic transition from normal colon epithelium to premalignant adenoma with the aid of an ‘adenoma–carcinoma sequence’ mouse CRC model induced by DMH. We generated a modified mouse CRC model induced by DMH for DNA sequences, and characterized the molecular networks. Data from 454 pyrosequencing of the V3- V5 region of the 16S rDNA gene and immunohistochemical detection of APC, P53, K-RAS and BRAF genes were assessed with Principal coordinates, UniFrac, and Kruskal-Wallis rank sum test. The inflammatory group showed enrichment of Bacteroidetes and Porphyromonadaceae (P < 0.01). OTUs affiliated with Firmicutes were enriched in the hyperproliferative group (P < 0.01). Rikenellaceae and Ruminococcaceae showed an increasing trend during the CRC process while the opposite pattern was observed for Prevotellaceaeand Enterobacteriaceae. OTUs related to Alistipes finegoldii were significantly increased during CRC development, P53, K-RAS and BRAF, were gradually increased (P < 0.05). Conversely, expression of APC was decreased during the course of development of CRC. Our results demonstrate that the biological evolutionary shift of gut microbiota, characterized by a gradual decrease in ‘driver’ bacteria and an increase in DNA damage-causing bacteria, is accompanied by tumor development in the CRC model. The synergistic actions of microbiota dysbiosis and effects of bacterial metabolites on related molecular events are proposed to contribute to the progression of CRC tumorigenesis.


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