Fig. 4

Potential mechanisms by which the gut microbial metabolite SCFAs augment the efficacy of ICI. A SCFAs inhibit the proliferation and induce the apoptosis of cancer cells. The butyric acid of SCFAs, a metabolite of Faecalibaculum rodentium PB1 and H. biformis, inhibits the activity of HDAC and the calcineurin-mediated activation of NFATc3 transcription factor, thereby blocking the proliferation of tumor cells. Propionic acid produced by A. muciniphila activates the cell cycle inhibitor p21 through GPR43 and downregulates the IAP inhibitor, which inhibits cancer cell proliferation, induces apoptosis, and improves the antitumor effect of ICI. B SCFAs improve the antitumor immune response. Butyrate can directly enhance CD8⁺ T cell antitumor cytotoxicity by inducing ID2 expression in CD8⁺ T cells through IL-12 signaling. Valeric acid and butyric acid of SCFAs promote expression of effector molecules such as IFNγ and TNFα and enhance the antitumor effects of CTLs. C SCFAs provide energy for immune cells. SCFAs provide energy to B cells, memory T cells, and effector T cells by regulating metabolic pathways such as glycolysis, the TCA cycle, and β-oxidation to enhance ICI efficacy