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.

Alterations of the Predominant Fecal Microbiota and Disruption of the Gut Mucosal Barrier in Patients with Early-Stage Colorectal Cancer

“…Previous studies showed that the actions of Enterobacteriaceae are similar to the prolonged inflammatory response induced by enterotoxigenic Bacteroides fragilis [33,34]. Sun et al has showed significant enrichment of Enterobacteriaceae in the DMH-induced CRC animal model [35]. They also found that Enterobacteriaceae showed higher relative abundance in the early stages of tumor formation, while it was gradually replaced with other bacteria such as Rikenellaceae, Lachnospiraceae, Ruminococcaceae, and Streptococcaceae BioMed Research International [35].…”

“…Sun et al has showed significant enrichment of Enterobacteriaceae in the DMH-induced CRC animal model [35]. They also found that Enterobacteriaceae showed higher relative abundance in the early stages of tumor formation, while it was gradually replaced with other bacteria such as Rikenellaceae, Lachnospiraceae, Ruminococcaceae, and Streptococcaceae BioMed Research International [35]. Another potential cancer-promoting bacterium, F. nucleatum, was associated with CRC.…”

Chronic nonbacterial prostate inflammation in a rat model is associated with changes of gut microbiota that can be modified with a galactoglucomannan‐rich hemicellulose extract in the diet

“…Inside these phyla, we found significant increases in the hormone‐treated rats in specific bacterial taxa previously linked to several diseases. Elevated Rikenellaceae levels have been previously suggested to be associated with premalignant colorectal adenoma and ulcerative colitis , whilst the members of the Clostridiaceae family have been linked to colitis and diabetes . Members of the Odoribacter have been described as an inhabitant of the human intestine and has the potential to become an opportunistic pathogen : increased Odoribacter levels have been shown to be linked with Alzheimer's disease , chronic stress and colorectal cancer .…”

The Intestinal Microbiota in Colorectal Cancer

“…This is of particular note, as several human metagenomic studies revealed an association between Alistipes and CRC (Feng et al, 2015). Alistipes finegoldii can be increasingly found in an ''adenoma-carcinoma sequence'' mouse CRC model induced by 1,2-dimethylhydrazine (Sun et al, 2017).…”