Gut Microbiome

Lactarius hatsudake Tanaka Polysaccharides Inhibit Hepatocellular Carcinoma by Modulating the Gut Microbiota and Its Metabolites.

TL;DR

These findings suggest that LHP-induced gut microbiota remodeling is associated with antitumor immune modulation.

Key Findings

LHP and fecal microbiota transplantation were associated with reduced hepatocellular carcinoma tumor growth.

  • The abstract states that LHP and fecal microbiota transplantation were associated with reduced tumor growth.
  • The study builds on the authors' earlier report that LHP can inhibit hepatocellular carcinoma.
  • The abstract does not give tumor size reductions, sample sizes, or p-values.

LHP intervention increased the CD8+/CD4+ T cell ratio and interferon-γ levels in tumor, spleen, and blood.

  • Increases were observed in three compartments: the tumor, the spleen, and the blood.
  • The abstract describes these as changes in the tumor immune microenvironment that paralleled attenuated hepatocellular carcinoma progression.
  • Quantitative values are not given in the abstract.

LHP treatment significantly increased beneficial bacteria such as Bifidobacterium animalis and reduced Lactobacillus murinus.

  • The changes were found in both in vivo and in vitro microbiome analyses.
  • The abstract reports the changes as significant but gives no effect sizes or p-values.

Metabolomic analyses suggested LHP may be metabolized into propionate via the succinate pathway.

  • The propionate production was accompanied by changes in microbial composition.
  • The abstract words this as a suggestion ('may be metabolized'), which indicates the evidence is inferential.

LHP-associated microbial and metabolite changes significantly inhibited the arginine and tryptophan metabolic pathways.

  • These microbial and metabolite changes paralleled improvements in the tumor immune microenvironment.
  • They also coincided with attenuated hepatocellular carcinoma progression.
  • The abstract reports associations rather than demonstrated causation.

The authors conclude that LHP-induced gut microbiota remodeling is associated with antitumor immune modulation.

  • The mechanism of LHP's anti-HCC effect, particularly gut microbe-mediated antitumor immunity, had previously been unclear.
  • The conclusion is framed as an association.

What This Means

This study looked at how a polysaccharide (a type of complex sugar) from the Lactarius hatsudake Tanaka mushroom, called LHP, might slow liver cancer. The researchers had previously shown that LHP can inhibit hepatocellular carcinoma. Here they asked whether gut bacteria are part of the explanation. Treatment with LHP, and transferring gut microbes from treated animals through fecal microbiota transplantation, were both associated with reduced tumor growth. LHP treatment shifted the gut microbial community. Bifidobacterium animalis, a bacterium generally considered beneficial, increased, while Lactobacillus murinus decreased. Metabolic analyses suggested LHP may be turned into propionate, a short-chain fatty acid, and that arginine and tryptophan metabolic pathways were suppressed. At the same time, immune measures improved. The ratio of CD8+ to CD4+ T cells and levels of interferon-γ, an immune-signaling molecule, rose in the tumor, spleen, and blood. This research suggests that a mushroom-derived polysaccharide could work against liver cancer partly by reshaping gut bacteria and their metabolites, which in turn may support anti-tumor immune activity. The findings are described as associations, and the abstract points to experimental (non-human) models, so they do not show that LHP would work as a treatment in people. Further research would be needed to confirm the mechanism and test safety and effectiveness.

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Citation

Chang S, Zha Y, Chen S, Xiao Y, Zhou Y, Tian Y, et al.. (2026). Lactarius hatsudake Tanaka Polysaccharides Inhibit Hepatocellular Carcinoma by Modulating the Gut Microbiota and Its Metabolites.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c06885