The Interactions Between Intestinal Microbiota Dysbiosis And Distant Metastasis Of Colorectal Cancer

Colorectal cancer(CRC)is one of the most common malignant tumor that threaten people's health.Studies have found that the oncogenesis of CRC is closely associated with the intestinal microbiota dysbiosis.However,compared with the long and complex process of CRC oncogenesis,which involve multiple genes,steps and stages,the progress and metastasis of CRC are relatively much faster.Clinical data showed that although treated with surgery or chemotherapy,many CRC patients would still enter into the advanced course.Although some studies witnessed microbial structure shifts among CRC patients,the relationship between intestinal microbiota and CRC metastasis is remain unknown.We hypothesized that the intestinal microbiota dysbiosis is an important factor that promote tumor metastasis.By comparing the intestinal microbial structure between metastatic and non-metastatic CRC patients,we try to prove the relationship between the intestinal microbiota and metastasis of CRC and if possible,find certain specific bacteria that plays a key role in cancer metastasis.A total of 27 patients with CRC 44?80 years of age were selected from the Secone Affiliated Hospital of Zhejiang University.All the stool samples were gathered prior to bowel cleansing.The disease was diagnosed by colonoscopy and biopsy.No metastases were found in 12 patients(assigned to Group P)and liver metastases were observed by hepatic enhanced CT or MRI in other 15 patients(assigned to Group M).No study subjects had diabetes,infectious diseases,diarrhea or astriction,history of multiple intestinal adenomas or particular diets.None of the subjects were taking medications at the time of sample collection,nor had they used antibiotics within at least one month of sample collection.The clinical characters between groups showed no significant difference.In Study ?,genomic DNA was extracted from all stool samples and the V1?V3 region of bacterial 16 S rDNA was performed by high-throughput sequencing.Both principal component analysis(PCA)and beta diversity analysis based on UniFrac metric showed that the intestinal microbial structures of metastatic CRC patients were similar with those of non-metastatic patients.Taxonomical assignments of OTUs were performed by using RDP clarifier in accordance with the Greengenes Database.There were 13 phyla in stool samples.Firmicutes and Bacteroidetes were the most dominant phyla in both groups.The phylum-specific relative abundance of microbiota sequences revealed no difference between groups.However,at the genus level,the abundance of Bacleroides,Clostridium,Faecalibacterium and Ochrobactrum were significantly higher in Group P,while the abundance of Atopobium,Coprococcus,Filifactor and Oxalobacter were found significantly higher in Group M.The decrease of intestinal butyrate-producing bacteria(BPB)is considered to be related with intestinal inflammation and tumorigenesis.Thus,in Study ?,we analyzed all BPB categories among all samples.7 BPB genus were found in both groups and the total quantity showed no significant difference between groups.We only found that Faecalibacterium is under-represented and Coprococcus about 4-fold higher in Group M.Based on the results of Study ? and ?,we concluded:1.There are no difference of intestinal microbial structures between metastatic and non-metastatic CRC patients.The abundance of several genus were different.Bacteroides,Clostridium,Faecalibacterium and Ochrobactrum were enriched in non-metastatic CRC patients,whereas Atopobium,Coprococcus,Filifactor and Oxalobacter was reduced.2.The distribution of category and quantity of BPB is of no difference between metastatic and non-metastatic CRC patients.Faecalibacterium is under-represented in Group M.As its sole known species,Faecalibacterium prausnitzii is supposed to take part in the progression and metastasis of CRC.