## 5 Liver Cancer
### Microbiota in HCC Liver Cancer  
An increasing amount of data indicates that microbiota plays a key role in HCC development. A study on mice exposed to chemical carcinogens revealed that oral administration of probiotics (i.e., _Lactobacillus_, or combinations of _Streptococcus thermophilus_ and _Bifidobacterium_) might slow down HCC development. It is believed that probiotics, by lowering serum LPS levels, enhance cancer development by alleviating chronic inflammation [103]. However, changes in gut microbiota composition are reported to promote HCC development. Research shows that gut microbiota of patients with advanced liver disease and cirrhosis are characterized by an increase in potentially pathogenic bacteria such as _Proteobacteria_, while the number of bacteria with beneficial properties is significantly reduced. This increased prevalence of pathogenic bacteria in the gut microbiota is associated with secretion of specific microbe-associated molecular patterns and substances. Combined with the excessive immune response triggered by microbial antigens, these harmful metabolites might lead to the development of liver fibrosis and genotoxicity [99,102]. It is well known that alcohol abuse is one of main causes of liver cirrhosis and cancer development. It is worth noticing that excessive alcohol consumption significantly influences the intestinal community of microbes. [PERSON] et al. reported that the intestinal microbiome of patients with alcoholic liver disease (ALD) had decreased a number of members of Bacteroidetes order, which are important butyrate-producing bacteria, as well as depletion in _Parabacyeroides_ genus, _Prevotella_, and _Clostridium_. Moreover, ALD-related microbiome was enriched in oral microbes (such as _Streptococcus constellatus_, _S. salivarius_, _Veillonella atypica_, _V. dispar_, and _V. parvula_) and, interestingly, _L. antri_, _crispatus_, _delbrueckii_, _oris_, _ultunensis_, and _B. animalis_ and _dentium_: members of _Lactobacillus_ and _Bifidobacterium genera_[110]. Moreover, it is believed that microbiota may influence HCC progression by contributing to the progression of viral hepatitis, one of the common causes of HCC development. [PERSON] et al. indicate a correlation between microbial translocation and the degree of liver disease in patients with chronic viral HBV or HCV infection [111]. An in vivo study conducted on mice with viral-induced liver disease found that germ-free mice were protected from HCC development in comparison with controls. These data suggest that HBV and HCV infection might promote HCC development in a microbiota-related manner [112]. HCC patients display a different gut microbiota composition to healthy subjects. Until now, most data report that changes in HCC-related microbiome comprise a decrease in beneficial bacteria taxa such as Lachnospiraceae, Ruminococcaceae, and Clostrridiales, and an increase in Enterobacteriaceaeae and Bacteriodaceae [113]. [PERSON] et al. reported a significant increase of Gram-negative bacterial strains in a mouse model of cirrhosis HCC [102] (murine model, immunochemistry). [PERSON] et al. reported that HCC-related gut microbiota differed from wo-HCC by different abundance of Firmicutes phylum (with an increase in _Erysipelotrichaceae_ and decrease in _Leuconostocaceae_ families), a decrease in Fusobacterium genus, and an increased ratio of bacteroides/prevotella [113]. It is being suggested that increased levels of circulating LPS and impairment of gut barrier integrity influence cancer development. High circulating levels of LPS have been noted in both animal models of carcinogen-induced hepatocarcinogenesis and HCC patients [5; 102]. An elevated LPS level is frequently associated with intestinal permeability and bacterial translocation and can cause pro-inflammatory activity in the liver [114]. Diet is also an important agent in hepatocarcinogenesis. [PERSON] et al. reported that dietary or genetic obesity leads to changes in gut microbiota composition, leading to an increase of deoxycholic acid (DCA) production.