Low Carbohydrate Diet Containing Soy Protein and Fish Oil Reduces AOM/DSS-Induced Colon Cancer, in Part, by an Acetate-Mediated Reduction in TH17 Cell Differentiation.

Since our previous studies found a low-carbohydrate (CHO) diet containing soy protein and fish oil (i.e., 15%Amylose/Soy/FO) significantly reduced tobacco carcinogen-induced lung nodules in A/J mice, breast tumors in C3(1)/Tag mice, and myelomalignancy in miR-146a knockout mice, we asked herein if this CHO diet could also reduce colorectal cancer. We tested the efficacy of the 15%Amylose/Soy/FO diet in preventing colitis-induced colorectal cancer using an azoxymethane/dextran sodium sulfate BALB/c mouse model. The 15%Amylose/Soy/FO diet significantly reduced colon tumor numbers compared to a Western diet and this was associated with a reduction in blood glucose, and a trend towards an increase in plasma β-hydroxybutyrate and an increase in liver fatty acid synthase, suggesting a systemic metabolic shift from glucose to fatty acids as an energy source. In addition, our CHO diet reduced proinflammatory cytokines, induced a marked change in the fecal microbiome, an increase in cecal and fecal acetate, and a reduction in interleukin-17A expressing cells in the colonic tumors of mice on the 15%Amylose/Soy/FO diet. Taken together, our results suggest the 15%Amylose/Soy/FO diet ameliorates colitis and prevents the subsequent development of colorectal cancer, in part by an acetate-mediated reduction in TH17 cell development.