Cell颠覆性发现：生酮饮食为何能抗癌，关键在于肠道微生物对饮食中植物化学物质的代谢

Core Viewpoint - The interaction between diet, phytochemicals, gut microbiome, and the liver significantly influences the anticancer activity of PI3K inhibitors, challenging previous assumptions about the role of macronutrients in this process [2][11]. Group 1: PI3K Inhibitors and Cancer Treatment - PI3K signaling pathway is crucial in insulin action and is frequently activated in human cancers, with approved PI3K inhibitors used for treating leukemia, lymphoma, and breast cancer [2]. - Preclinical studies indicate that ketogenic diets can enhance the efficacy of PI3K inhibitors in cancer treatment, although the underlying mechanisms were previously unclear [2][5]. - A recent study published in Cell reveals that the synergistic anticancer effect of ketogenic diets and PI3K inhibitors is not related to macronutrient composition but rather to the metabolism of dietary phytochemicals by gut microbiota [3][7]. Group 2: Role of Diet and Gut Microbiome - Dietary interventions can influence disease progression and drug response, with various diets shown to slow tumor growth and enhance anticancer drug activity in preclinical models [5]. - The study highlights that the differences in diets extend beyond macronutrient composition, emphasizing the importance of phytochemicals and their interactions with gut microbiota [6][8]. - Gut microbiota can metabolize phytochemicals from the diet, leading to the production of metabolites that affect drug metabolism and efficacy [7][9]. Group 3: Key Findings of the Study - Purified rodent diets can sensitize tumors to PI3K inhibitors independently of macronutrient composition [9]. - The sensitizing effect involves changes in drug metabolism by liver cytochrome P450 enzymes [9]. - Specific phytochemicals, such as soyasaponins, are metabolized by gut microbiota into compounds that can reduce the levels and activity of PI3K inhibitors [9][11].