Table 3.
Anti-tumorigenic microbes and metabolites in HCC.
| Type | Agent | Key protective mechanisms | Evidence level |
|---|---|---|---|
| Beneficial bacteria | Bifidobacterium spp. | Maintains barrier integrity; suppresses oncogenes (miR-155, miR 221, KRAS); reduces inflammatory cytokines | Preclinical (human correlation) |
| Lactobacillus spp. (including L. acidophilus, L. rhamnosus GG, L. casei) | Enhances tight junctions; promotes tumor suppressor genes (miR-122, PU.1); modulates JAK/STAT and TLR/NF-κB pathways | Preclinical (human correlation) | |
| Akkermansia muciniphila | Correlated with ICI sensitivity; mucus layer maintenance | Human & Preclinical | |
| Verrucomicrobiaceae, Bifidobacteriaceae | Reduced in HCC; associated with barrier function | Human data | |
| Alistipes, Dialister, Collinsella, Adlercreutzia | Depletion linked to immune dysregulation | Human data | |
| Prevotella, Oscillibacter | Propionate production; regulate Treg/IL-10 homeostasis | Preclinical | |
| Bacteroides thetaiotaomicron | Acetic acid secretion; enhances CD8 + T cell function | Preclinical | |
| Beneficial bacteria | Lachnoclostridium | Enrichment increases secondary bile acids beneficial for ICI response | Human data |
| Elusimicrobium, Christensenellaceae, R-7Elusimicrobium, Christensenellaceae R-7 | Positively correlated with DAA treatment outcomes in HCV patients | Human data | |
| Protective metabolites | Short-chain fatty acids (SCFAs) | Butyrate: Maintains barrier integrity; inhibits HDAC; promotes p53 activation and apoptosis | Human&Preclinical |
| Acetate: Enhances CD8 + T cell function; inhibits pro-inflammatory factors via GPR41/43 | Preclinical | ||
| Propionate: Inhibits TNF and iNOS; reduces intestinal inflammation | Preclinical | ||
| General: Induces Treg differentiation; increases FOXP3 expression; suppresses TLR4/NF-κB pathway | Human & Preclinical | ||
| Protective metabolites | Primary bile acids & FXR agonists | Maintain intestinal barrier; reduce bacterial translocation; inhibit inflammation | Human & Preclinical |
| Polyphenolic compounds | Inhibit NF-κB pathway; reduce inflammation and proliferation | Preclinical | |
| Antimicrobial peptides | Enhanced chemical barrier function | Preclinical |
ICI, immune checkpoint inhibitor; SCFA, short-chain fatty acids; HDAC, histone deacetylase; Treg, regulatory T cell; GPR, G protein-coupled receptor; TNF, tumor necrosis factor; iNOS, inducible nitric oxide synthase; DAA, direct-acting antiviral; HCV, hepatitis C virus; FXR, farnesoid X receptor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; IL, interleukin. Evidence Level: Human data—findings from clinical studies or epidemiological research; Preclinical—evidence from in vitro or animal model studies; Human & Preclinical—convergent evidence from both human and experimental studies. Note: Specific strains within genera may exhibit varying effects; efficacy is context-dependent and influenced by host factors, disease stage, and baseline microbiome composition.