EXTH-30. THERAPEUTIC BENEFIT OF A KETOGENIC DIET THROUGH ALTERED GUT MICROBIOTA IN A MOUSE MODEL OF GLIOMA

Like many cancers, glioma cells have an altered metabolic state and utilize glycolysis even in the presence of oxygen, and thus require a large amount of glucose. The ketogenic diet is a high fat, low carbohydrate, low protein diet that limits the amount of glucose, and theoretically starves tumor growth. In addition, recent reports have indicated that the gut microbiome can influence tumor growth as well as the effectiveness of certain therapeutic agents. In this study, we sought to determine if the ketogenic diet is an effective treatment for glioma, and to correlate changes in the healthy gut bacteria in response to the ketogenic diet. In an orthotopic mouse model of glioma, we found that mice fed the ketogenic diet had slightly increased survival compared to mice fed a normal diet. Comparing the composition of gut bacteria from animals on normal versus ketogenic diets, we found significant differences in several key microbes. Interestingly, we observed that there were several long-term ketogenic survivors implanted with intracranial tumors and displayed a significant increase in the percentage of microbes found in the murine gastrointestinal tract (F. rodentium and related microbes). We found that F. rodentium growth does not occur until day 21 on the diet; thus, F. rodentium could be introduced early as a probiotic and enhance anti-tumor effects of the ketogenic diet. Additionally, we found that the ketogenic diet increased the percentage of mature Th17 cells, potentially collaborating with the growth of F. rodentium to decrease tumor growth. No studies have ever evaluated a probiotic for therapeutic efficacy in glioma. As the ketogenic diet is very strict, and can negatively affect quality of life, a ketogenic-diet probiotic (healthy gut bacteria, similar to the probiotics in yogurt) may offer an alternative supplement and patients could possibly eat a modified (less strict) ketogenic diet.