Significance Hepatocellular carcinoma is the second most deadly cancer type globally, requiring the development of alternative or complementary therapeutic and prophylactic methods. Here, when feeding a mouse model with a novel probiotic mixture 1 wk before the tumor inoculation, we observed a reduction of the tumor weight and size by 40% compared with the control. Our results revealed that the probiotics’ beneficial effect is closely related with the abundance of certain beneficial bacteria that produce antiinflammatory metabolites, which subsequently regulate the proinflammatory immune cell population via the crosstalk between gut and tumor. We believe that our study highlights the extraordinary potential of probiotics in extraintestine cancers and can be adapted to the study of other cancers.
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