Therapeutic potential of Lactobacillus kefiranofaciens ZW18 postbiotic in alleviating hepatocellular carcinoma.

Metabolomics analysis revealed that the L. kefiranofaciens ZW18 postbiotic (Post18) contains compounds with potential anticancer properties.

• Metabolomics was used to characterize Post18 composition.
• Post18 was found to contain c-di-GMP and 3-hydroxybutyric acid, both identified as compounds with potential anticancer properties.
• Post18 is a derivative of the probiotic Lactobacillus kefiranofaciens ZW18.

Post18 effectively inhibited HCC cell proliferation and migration in vitro.

• Cell experiments demonstrated that Post18 inhibited hepatocellular carcinoma cell proliferation.
• Post18 also inhibited HCC cell migration in vitro.
• Post18 induced apoptosis in HCC cells.

Post18 supplementation significantly inhibited tumor growth in an ectopic HCC mouse model.

• The antitumor effect of Post18 was verified in an ectopic hepatocellular carcinoma model.
• Post18 supplementation significantly inhibited tumor growth.
• Post18 reduced the proportion of proliferating cells within the tumor.

Post18 enhanced immune cell infiltration and pro-inflammatory cytokine production in the tumor microenvironment.

• Post18 supplementation enhanced the infiltration of CD4+ and CD8+ T lymphocytes into tumors.
• Post18 elevated the production of pro-inflammatory cytokines IFN-γ and TNF-α.
• These effects collectively improved the tumor microenvironment.

Post18 modulated immunosuppressive and cytotoxic immune markers in the spleen of HCC mice.

• Post18 decreased the relative transcript levels of FoxP3 in the spleen, suggesting reduced number or function of immunosuppressive regulatory T cells (Tregs).
• Post18 increased the relative transcript levels of GzmB (Granzyme B) in the spleen, suggesting activation of cytotoxic immune responses.
• These splenic immune changes suggest Post18 reduced immunosuppression and activated antitumor immune responses in HCC mice.

Post18 promoted the growth of beneficial gut microorganisms in HCC mice.

• Post18 supplementation increased the relative abundance of beneficial microorganisms including Dubosiella, Lactobacillus, and Lachnospiraceae_NK4A136_group.
• These microorganisms are associated with production of beneficial metabolites.
• The promoted microbes likely contributed to the antitumor effects observed.

Post18-promoted gut microbiota produced beneficial metabolites, particularly short-chain fatty acids including butyric acid, which likely contributed to antitumor effects.

• The beneficial gut microorganisms promoted by Post18 produced SCFAs (short-chain fatty acids).
• Butyric acid was specifically identified as a key SCFA metabolite produced.
• These metabolites were suggested to contribute to the antitumor effects of Post18 supplementation.