How the Ketogenic Diet Shapes the Microbiome to Influence Cancer Immunotherapy Outcomes: An Exploration of Clinical Trials and Their Results

Ketogenic dietary interventions (KDIs) are increasingly explored as adjuncts in oncology due to their metabolic and immunomodulatory effects. One mechanism by which KDIs are expected to modulate the immune system is by altering the gut microbiome, which has been shown to affect treatment outcomes, particularly in the context of immunotherapies. This review synthesized findings from 43 clinical trials to evaluate the current landscape of KDIs in cancer care, with a focus on the gut microbiota and immunotherapy. Although 47% of identified trials are completed, none have yet published results combining KDIs with immunotherapy. Since 2020, however, there has been a significant increase in ongoing studies investigating this combination and incorporating microbiome endpoints. While KDIs may help shape an immunotherapy-permissive environment, further clinical evaluation is necessary to determine the full extent of KDIs on the microbiome. Future research should prioritize longitudinal microbiome profiling and standardized adherence reporting to clarify the therapeutic potential of KDIs as a metabolic adjuvant to immune checkpoint inhibitors.