Metagenomic Comparison Of Microbiota In Patients With Colorectal Cancer Treated By Surgery Or Chemotherapy

OBJECTIVE:Colorectal cancer(CRC)is one of the most common cancers which happens in the digestive tract.In recent years,it has been found that intestinal microbiota disorders play an important role in the development of this cancer.The study intends to analyze the clinical mechanism of structural changes of intestinal flora in healthy people and CRC patients treated with/without chemotherapy or surger,and to also find potential microbial biomarkers.The study will provide certain clinical application value for improving the effect of CRC treatment,reducing the rate of chemotherapy resistance and reducing the side effects duiring treatment.METHODS:A total of 69 fecal samples were collected and divided into 4 groups.There were 33 healthy individuals(group C),17 CRC patients(group I),5 CRC patients treated with surgery(group IO),and 14 chemotherapy patients(group D).After recording their clinical markers,DNA from the 69 fecal samples was extracted,and the V4V5 region of 16S rRNA was sequenced by high-throughput sequencing on Illumina HiSeq2500 platform.Bioinfonnatics analysis was performed to obtain the information of intestinal microbial community structure and relative abundance,and to find the different flora among different groups.RESULTS:According to bioinformatics analysis,we obtained 1259 OTUs in the four groups on average.Species annotation results show that the main enrichment species in groups C,I and D are Bacteroidetes and Firmicutes,and there are some species imbalance in groups I and D compared to group C.In contrast,the IO group treated with surgery underwent a dramatic change in community structure,with the dominant species turning to be Proteobacteria.At the species level,B.ovatus was abundant in the healthy control group,but the relative abundance was reduced in the CRC group and the D group,but not detected in the IO group.The four groups cluster to each other according to PCoA analysis.The alpha diversity indexes Chao and Shannon of intestinal microbiome were both higher than those of the IO group,indicating that surgery greatly affected the intestinal microbiome structure of CRC patients.PERMANOVA analysis also showed significant differences in community structure between these groups.CONCLUSION:Surgery has a profound impact on the intestinal microbial structure of CRC patients.The microbial diversity of the group IO decreased sharply,and the species of dominant bacteria also changed compared with the other three groups.B.ovatus was abundant in healthy controls,but its relative abundance was decreased in group I and group D,but not in group IO,suggesting that this species could be a potential target for diagnosis and treatment of CRC.In addition,other potential biomarker species including Fusobacterium nucleatum,Sutterella,Veillonella dispar were found in this study.These specific microorganisms may serve as biomarkers for noninvasive diagnosis of CRC.