Table 2.

Pro-oncogenic microbes and metabolites in HCC.

Type	Agent	Key mechanisms	Evidence level
Pro-oncogenic bacteria	Streptococcus maltophilia	Associated with poor prognosis	Human data
	Proteobacteria (phylum)	Increased abundance in HCC	Human data
	Actinobacteria (phylum)	Increased abundance in HCC	Human data
	Parabacteroides, Clostridium, Gemmiger	Marked increase; linked to inflammation and fibrosis	Human data
	Phascolarctobacterium, Enterococcus	Elevated in HCC patients	Human data
	Klebsiella pneumoniae	Translocation to liver; promotes HCC	Preclinical
	Escherichia coli	LPS production; TLR4 activation	Preclinical
	Rhizobiaceae, Agrobacterium	Enrichment defines HCC signatures	Human data
	Bacteroides (in specific contexts)	Associated with MDSC elevation	Human data
Harmful metabolites	TMAO	Activates POSTN/AKT/mTOR pathway;promotes proliferation and invasion	Preclinical (human correlation)
	Secondary bile acids (deoxycholic acid)	Induces ROS, DNA damage, hepatic stellate cell senescence; activates TLR2	Preclinical (human correlation)
	Lipopolysaccharide (LPS)	Activates TLR4/MyD88/NF-κB; chronic inflammation	Human & Preclinical
	Lipoteichoic acid	Synergy with bile acids; upregulates COX-2	Preclinical
	Reactive oxygen species (ROS)	DNA damage, mitochondrial dysfunction, epigenetic alterations	Preclinical

HCC, hepatocellular carcinoma; TMAO, trimethylamine N-oxide; LPS, lipopolysaccharide; TLR, Toll-like receptor; ROS, reactive oxygen species; MDSC, myeloid-derived suppressor cells; POSTN, periostin; AKT, protein kinase B; mTOR, mechanistic target of rapamycin; COX-2, cyclooxygenase-2; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells. Evidence Level: Human data—findings from clinical studies or epidemiological research in human subjects; Preclinical—evidence from in vitro or animal model studies; Human correlation—preclinical mechanisms with supporting human correlational data.