| ?Background and objective?Increasing evidences suggest that liver diseases are closely related to changes in gut microbiota.The disorders and translocation of gut microbiota can stimulate the changes of inflammatory factors and inflammation.Inflammatory responses not only induce tumor formation,but also promote the development and metastasis of tumors.Gut dysbiosis is closely related to the development of various diseases,and more and more bacteria related metabolites are involved in the development of diseases.The participation of intestinal metabolites in host immunity,signal transduction and epigenetic regulation is the main reason.Changes in the intestinal microbial environment cause inflammation in the liver while continuous inflammatory stimulation causes liver signal transduction disorders and thus leads to more serious liver diseases.Inflammation associated with liver damage is increasingly considered as a major risk factor for liver cancer.By using metagenomics analysis on 16 S rRNA gene,we found the differences in gut microbiota,gut dysbiosis and related function of signaling pathways between HBV induced HCC(HBVC)and non HBV induced HCC(NHBVC).It is essential for us to better understand the pathogenesis of liver cancer and find more effective and predictive method.?Materials and Methods?A total of 57 HCC patients and 33 healthy controls who attended annual physical examination were recruited from September 2016 to March 2017 at Nanjing Medical University Affiliated Cancer Hospital.The HCC patients were divided into two groups: patients with HBV were defined as HBV induced HCC(HBVC),patients without HBV defined as Non-HBV induced HCC(NHBVC).Moreover,patients' information including clinical features,pathology features,laboratory examination indexes were obtained from the medical records.By using comprehensive 16 SrRNA analyses,predicated KEGG pathways and statistical analysis method,we aimed to explore the development of liver cancer associated with gut microbiota.?Results?1.The feces of NHBVC patients harbored more pro-inflammatory bacteria (such as Escherichia-Shigella,Enterococcus,Proteus,Veilonella),and reduced levels of Faecalibacterium,Ruminococcus,Ruminoclostridium which resulted in a decrease in potentially anti-inflammatory SCFAs.A group of potentially anti-inflammatory bacteria increased in fecal of HBVC patients.Among them some gut microbiota markers can be complementary to clinical detection of HCC.2.Distinct differences in bacteria diversity were observed in the fecalmicrobiota between NHBVC and HBVC patients.The species richness of the fecal microbiota in HBVC patients were much higher than other two groups.3.The aberrant network of gut microbiota in NHBVC and HBVC patients were significantly different.NHBVC patients had a simpler concurrent network while the HBVC patients had an extremely complicated and small network.4.Predicted functional profiling suggests that the potential of NHBVC patients associated with KEGG pathways is different from HBVC patients.The feces of NHBVC patients had relatively lower abundance in pathway related to amino acid and glucose metabolism,but some types of transport or secretion presented more.However,the HBVC patients had the opposite results of bacterial composition and predicated KEGG pathways.?Conclusions?Our study suggested an association of HBV or Non-HBV induced HCC with different microbiota and network.We suggested that modification to the microbiota as part of adjuvant therapy.Our data also provides additional evidence on the importance of the different microbiota in tumorigenesis of both HBVC and NHBVC patients.The clinical settings in which targeting the gut-microbiota-liver axis for the prevention of disease progression and HCC development seems promising. |
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