title: Evolutionary biologic changes of gut microbiota in an 'adenoma-carcinoma sequence' mouse colorectal cancer model induced by 1, 2-Dimethylhydrazine.
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.
authors.affiliation: Department of General Surgery, Qingdao municipal hospital, Qingdao, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Shanglong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Yantai Yuhuangding Hospital, Yantai, China.
authors.forename: Zengwu
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Epidemiology and Health Statistics, Qingdao University Medical College, Qingdao, China.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Shougen
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of General Surgery, Zhucheng People's Hospital, Weifang, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lian
authors.affiliation: Department of General Surgery, Linzi District People's Hospital, Zibo, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D003106:Colon / Q000382:microbiology*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D004249:DNA Damage; D004269:DNA, Bacterial / Q000235:genetics; D018450:Disease Progression; D064806:Dysbiosis / Q000382:microbiology / Q000473:pathology; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000139:chemically induced; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D016159:Tumor Suppressor Protein p53; C000613192:adenomatous polyposis coli protein, mouse; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D019813:1,2-Dimethylhydrazine
keywords: animal model; colorectal cancer; microbiology