Association Of Gut Microbiota With Hepatocellular Carcinoma And Its Effect And Mechanism On Liver Injury

Liver disease is prevalent in the world.It is the most common cause of death.About 300 million people in our country suffered from liver diseases,which seriously affect national health.To treat these diseases,the government bears a huge financial burden.Liver is the largest metabolic organ and one of the most important immune organ.As the liver receives the majority of its blood supply directly from the microbiota laden gut,via the portal vein,inherently the host microbiome and the liver become intimately linked.More and more evidences show that gut microbiota is highly related to health and disease,especially to the liver diseases.The liver impacts,and communicates with,the microbiota through hepatic mediators,such as bile acids or inflammatory signals.The gut microbiota and its metabolites,such as lipopolysaccharide and short chain fatty acids(SCFAs),control liver and metabolic functions.The dysbiosis impacts the metabolic functions of liver,which leads to metabolic syndrome and hepatic steatosis which develops into hepatic fibrosis or even hepatoma.End-stage liver disease is associated with severe dysbiosis,which leads to bacterial translocation and endotoxemia,resulting in immune activation and eventual hepatic injury as well as systemic inflammation.Therefore,gut microbiota may be an auxiliary tools for diagnosis of liver diseases.Amelioration of the dysbiosis could be a potential method to treat liver diseases.In this study,we compared the differences in the fecal microbiota of patients with primary hepatocellular carcinoma(HCC),metabolic syndrome,as well as healthy subjects through high-throughput sequencing of 16S rRNA gene amplicons.Our results showed that a significant difference of the gut microbiota was detected between the subjects with HCC and those without HCC.Although metabolic syndrome could interfere with gut microbiota,it was still impossible to cover up gut microbiota changes caused by HCC.Forty-nine bacterial genera of the 494 detected genera were detected significant differences between groups and might be used as an auxiliary tool for clinical diagnosis of HCC.In animal experiments,clindamycin and kanamycin were used to inhibit Gram-positive bacteria and Gram-negative bacteria in the gut microbiota of rat respectively.Probiotics were also used to regulate the composition of microbiota in rats.These treatments were used to assess the risk of chemical(diethylnitrosamine)induced liver injury in rats.The results showed that Gram-negative bacteria might aggravate the severity of chemical induced liver injury in rats,the Gram-positive bacteria in probiotics seemed protective against this effect despite gender differences.We also detected several phyla related to liver injury by analysing the microbiota in rats with different treatments.The structure of gut microbiota has a profound effect on chemical induced liver injury in rats.Manipulation of microbiota seems to be an promising therapy for liver injury.This study may help us to deepen our understanding the impact of gut microbiota on liver diseases.Gut microbiota-targeted biomarkers represent potential noninvasive tools for diagnosis of HCC.Gut microbiota is also a therapeutic target in the pathogenesis and the treatment of chronic liver disease by manipulating the microbiota structure through the application of antibiotics and probiotics.The results of this study are expected to provide forceful evidence for the application of gut microbiota in clinical practice in the future.