Colorectal Cancer Associated Microbiota And Its Interaction With The Host

Part â…  Diversity of colorectal cancer associated microbiotaIncreasing evidence suggests that gut microbiota are involved in the progression of colorectal cancer (CRC). We analyzed the overall structure of microbiota in patients with colorectal cancer and in healthy controls by pyrosequencing16S rRNA genes. The microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue were studied. Mucosa-adherent microbial composition was also surveyed by using rectal swab samples because the structure of the tissue-adherent bacterial community may be altered by bowel cleansing. We found that the microbial structure of the intestinal lumen and cancerous tissue significantly differed. Phylotypes that enhance energy harvest from diets or have metabolic exchange with the host were more abundant in the lumen. There were more Firmicutes and fewer Bacteroidetes and Proteobacteria in lumen. The overall microbial structure of cancerous tissue and noncancerous tissue was similar, although the tumor microbiota was less diverse. The structures of intestinal lumen microbiota and mucosa-adherent microbiota in CRC patients were different from matched microbiota in healthy individuals. Lactobacillales was enriched in cancerous tissue, yet Faecalibacterium was reduced. In the mucosa-adherent microbiota, Bifidobacterium, Faecalibacterium, and Blautia were reduced in CRC patients. Fusobacterium, Porphyromonas, Peptostreptococcus, and Mogibacterium were enriched in patients. In the lumen, predominant phylotypes Erysipelotrichaceae, Prevotellaceae, and Coriobacteriaceae, which are all related to metabolic disorders or metabolic exchange with the host, were increased in patients. Coupled with previous reports, such results imply that intestinal microbiota have association with CRC risk, and intestinal lumen microflora may influence CRC risk through cometabolism or metabolic exchange with the host. However, it is possible that the mucosa-associated microbiota affects CRC risk largely through direct interaction with the host.Part II Interaction mechanism between host and microbeMicroarray have been widely used for studying cellular responses of bacterial stimuli. In order to explore the host responses to bacteria, we investigated the gene expression profiles of mouse intestinal epithelial cell with Affymetric genechip. We found the genes associated with innate immune response process such as inflammatory and anti-bacteria response are strongly activated in the intestinal epithelial cell infected with Salmonella. And interleukin22mRNA was highly induced in the intestine lamina propria infected with Salmonella. Cell proliferation rate detemiined by MTT assay showed on stimulation with lower doses of IL22, there was an increase in cell proliferation whereas on stimulation with high doses of IL22a decrease of cell proliferation was observed. Such results were satisfied with the fact that under different environmental cues, IL22may have pathological role or protective role on host. Finally, we explored methods for isolation of dendritic cells from intestinal lamina propria. Such studies lay a good foundation for investigation the role of specific microbial community on colorectal cancer progression.