Zhifu Zhang

A ketogenic diet characterized by high fat and low carbohydrate can drive the body to produce a large number of ketone bodies, altering human metabolism. Unlike normal cells, tumor cells have difficulty in consuming ketone bodies. Therefore, the application of ketogenic diets in cancer therapy is gaining attention. However, the effect of ketogenic diets on body parameters of cancer patients is not well established. This meta-analysis aimed to summarize the effects of ketogenic diets on cancer patients in earlier controlled trials. PubMed, Embase, and Cochrane Library were searched for clinical trials that enrolled cancer patients who received ketogenic diets intervention. Ten controlled trials were included in this meta-analysis. Data were extracted and checked by three authors independently. Pooled effect sizes revealed a significant effect of ketogenic diets on body weight (SMD −1.83, 95% CI −2.30 to −1.35; p < 0.00001) and fat mass (SMD −1.52, 95% CI −1.92 to −1.07; p < 0.00001). No significant effect on blood glucose, insulin, or lipid profile except triglycerides was found in the analysis. It had no effect on liver and kidney function except that GGT were decreased a little. There were no significant changes in IGF-1 and TNF-α related to tumor growth. Mental health improvement of cancer patients was supported by several trials. Taken together, findings in this study confirmed that the ketogenic diet was a safe approach for cancer patients reducing body weight and fat mass. In addition, cancer treatment-related indicators changed insignificantly. Ketogenic diets may be beneficial to the quality of life of cancer patients. However, intervention duration in most studies is shorter than 6 months, and the effect of a long-term ketogenic diet is still required further validation. More trials with a larger sample size are necessary to give a more conclusive result; PROSPERO registration number: CRD42021277559.

The human gut is inhabited by hundreds of billions of commensal microbiota that collectively produce thousands of small molecules and metabolites with local and systemic effects on the physiology of the host. Much evidence from preclinical to clinical studies has gradually confirmed that the gut microbiota can regulate anti-tumor immunity and affect the efficacy of cancer immune checkpoint inhibitors (ICIs) therapy. In particular, one of the main modes of gut microbiota regulating anti-tumor immunity is through metabolites, which are small molecules that can be transported in the body and act on local and systemic anti-tumor immune responses to promote ICIs immunotherapy efficacy. We discuss the functions of microbial metabolites in humans, focusing on the effects and mechanisms of microbial metabolites on immunotherapy, and analyze their potential applications as immune adjuvants and therapeutic targets to regulate immunity and enhance ICIs. In summary, this review provides the basis for the rational design of microbiota and microbial metabolite-based strategies of enhancing ICIs.