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

Hepatocellular carcinoma (HCC) poses a global public health challenge due to its high mortality rate and poor prognosis. Intestinal flora exerts a crucial influence on its occurrence and development. The modulation of the gut microbiota by probiotics to alleviate cancer has been extensively studied. Postbiotics, derivatives of probiotics, are gaining attention as a novel therapeutic strategy for cancer due to their stability and safety. This study used metabolomics to show that the Lactobacillus kefiranofaciens ZW18 postbiotic (Post18), which contains compounds such as c-di-GMP and 3-hydroxybutyric acid with potential anticancer properties, possesses anticancer potential. Cell experiments demonstrated that Post18 effectively inhibited HCC cell proliferation and migration; it also induced apoptosis in HCC cells. This effect was verified in an ectopic HCC model, where supplementation with Post18 significantly inhibited tumor growth, reduced the proportion of proliferating cells, enhanced the infiltration of CD4+ and CD8+ T lymphocytes, elevated the production of pro-inflammatory cytokines (IFN-γ and TNF-α), and improved the tumor microenvironment. Additionally, Post18 decreased the relative transcript levels of FoxP3 and increased those of GzmB in the spleen, suggesting that Post18 reduced the number or function of immunosuppressive Tregs and activated immune responses in HCC mice. These effects may be linked to the promotion of beneficial microorganisms, including Dubosiella, Lactobacillus, and Lachnospiraceae_NK4A136_group, in the gut by Post18. In turn, these microbes produced beneficial metabolites such as SCFAs, particularly butyric acid, which likely contributed to the antitumor effects. Overall, Post18 supplementation represents a potential strategy for alleviating HCC and provides a foundation for developing additional treatment options.