Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics

Table 2 Therapeutics, gut microbiome, role in liver cancer

Study	Agents	Population	Outcomes
Animal models
Borges Haubert et al[64], 2015, Nutr Metab Insights	Prebiotics fructoligosaccharides	NAFLD rat model	Decreased liver fat via decreased lipogenesis
Liu et al[65], 2020, J Nutr Biochem	Probiotic Lactobacillus rhamnosus	Mouse model of liver disease (HFD)	Reduced NASH frequency, reduced steatosis inflammation and apoptosis in liver
Zhou et al[56], 2017, Sci Rep	FMT	Mouse model of liver disease (HFD)	Decreased hepatic lipid and proinflammatory cytokines, increased lactobacillus, improved gut barrier function, reduced endotoxemia, increase butyrate
Yoshimoto et al[33], 2013, Nature	Vancomycin	Mouse model of liver disease (HFD)	Reduced liver cancer
Janssen et al[58], 2017, Lipid Res	Antibiotics (ampicillin, neomycin, vancomycin and metronidazole)	Mouse model of NAFLD	Decreased secondary bile acids, decreased liver inflammation and fibrosis
Friedman et al[63], 2018, Gastroenterology	FXR agonist obeticholic acid	Mouse model of NAFLD	Decreased endogenous bile acid; Increased bacterial profile with Gram + including Firmicutes
Humans studies
Yang et al[5], 2020, Br J Nutrition	Diet and incident cancer risk- summary of studies	Worldwide epidemiologic studies of diet and liver cancer risk	Higher risk for liver cancer: Red Meat, Added Sugar, Processed food; Lowered risk for liver cancer: Vegetables, Fruits, Omega 3 oil, Coffee
Monem et al[55], 2017, Euroasian J hepatogastro	Probiotics Lactobacillus	NAFLD patients	Decreased AST and ALT
Bomhof et al[54], 2019, Eur J Nutrition	Prebiotic Oligofructose	NASH patients	Decreased hepatic inflammatory markers, deceased weight, improved glucose tolerance, decreased steatosis, decreased clostridium cluster XA and I and enhanced Bifidobacterium
Vrieze et al[57], 2012, Gastroenterology	FMT trial	FMT from lean donor to individuals with metabolic syndrome	Improved insulin sensitivity, Increase in butyrate producing bacteria

Selected studies (animal and human) of microbiome modulating therapies tested in non alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) with emphasis on NASH HCC. NASH: Non alcoholic steatohepatitis; NAFLD: Non alcoholic fatty liver disease; HCC: Hepatocellular carcinoma; FMT: Fecal microbiota transplant; PD-1: Programmed death-1; FXR: Farnesoid X receptor.