Gut microbiota contribution to hepatocellular carcinoma manifestation in non-alcoholic steatohepatitis

Table 2 Animal models investigating gut microbiota composition in nonalcoholic fatty liver disease induced hepatocellular carcinoma

Ref.	Experimental animal	Participants (groups)	Main findings
Xie et al[12]	Mice	Mice with STZ-HFD induced NASH-HCC; Control group	STZ-HFD group exhibited lower α-diversity than controls; The most abundant species in both control group and STZ-HFD group were primarily from the Bacteroides genus; The most decreased in abundance in the STZ-HFD group were Parasutterella spp., Bacteroides acidofaciens, Odoribacter spp., Barnesiella spp., Moryella spp., Paraprevotella spp., Lactobacillus intestinalis, and Akkermansia spp; Atopobium spp., Bacteroides acidifaciens, Bacteroides spp., Bacteroides uniformis, Bacteroides vulgatus, Clostridium cocleatum, Clostridium xylanolyticum, and Desulfovibrio spp. were significantly positively correlated with LPS in plasma, liver and feces; As most Bacteroides and Desulfovibrio were LPS-producers, LPS concentration was significantly increased in the STZ-HFD group.
Carter et al[21]	Mice	Western diet only (high fat and fructose diet, no CCl4 injection); CCl4 only (CCl4 injection intraperitoneal once a week and normal diet); NASH-HCC (Western diet and CCl4 injection intraperitoneally once a week); Control group (normal diet, no CCl4 injection);	NASH mice display impaired intestinal barrier function, leading to increased leakage of bacterial byproducts such as LPS into the circulation; NASH mice had reduced alpha diversity; Expansion of Erysipelotrichales was only observed in NASH mice
Zhang et al[22]	Mice	HFHC-fed mice (NAFLD-HCC group); HFHC-fed mice; Normal diet-fed mice (control group).	The microbiota composition changed during NAFLD-HCC formation: Mucispirillum, Desulfovibrio, Anaerotuncus were sequentially increased; Gut bacterial metabolites alteration like TCA and IPA were increased in NAFLD-HCC mice; Lower bacterial diversity and increased bacterial richness were observed in HFHC-fed mice with HCC than HFLC diet-fed mice with only steatosis; LPS concentration was elevated in HFHC-fed mice compared to HFLC-fed mice.

HCC: Hepatocellular carcinoma; HFHC: High-fat/high-cholesterol; HFLC: High-fat/low-cholesterol; IPA: Indole-3-propionic acid; LPS: Lipopolysaccharides; NAFLD: Non-alcoholic fatty liver disease; STZ-HFD: Streptozocin-high-fat diet; TCA: Trichloroacetic acid.