Associations of Low-Carbohydrate High-Fat Dietary Patterns with Colorectal Tumor Burden and Gut Microbial Dynamics in...

Malignant tumors require substantial energy sources for proliferation, and dietary composition may influence colorectal carcinogenesis through metabolic and microbiome-related mechanisms. This study investigated the association of low-carbohydrate high-fat dietary patterns with macroscopic tumor burden, morphologic inflammatory cell infiltration, and gut microbiome alterations using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of colitis-associated colorectal cancer. Male C57BL/6 mice received AOM followed by three cycles of DSS and were fed a standard diet (SD), high-carbohydrate diet (HCD), low-carbohydrate high-fat lard-based diet (HFL), or low-carbohydrate high-fat coconut oil-based diet (HFC). Body weight, colon length, splenic weight, macroscopic tumor formation, hematoxylin and eosin (H&E)-based inflammatory cell infiltration, and gut microbiome composition were analyzed. The HFL and HFC groups exhibited higher body weights and relatively preserved colon lengths compared with the SD and HCD groups. Tumor number and total tumor size were reduced in the HFL and HFC groups. Total lymphocyte-like inflammatory cell infiltration was not increased in the high-fat diet groups, whereas per-tumor values were interpreted cautiously because they are affected by tumor number. Gut microbiome analysis demonstrated altered microbial composition, increased alpha diversity, and distinct temporal microbial dynamics in the high-fat diet groups. Because the HFL and HFC diets simultaneously changed carbohydrate content, fat content, fat source, and caloric density, these findings should be interpreted as exploratory effects of low-carbohydrate high-fat dietary patterns rather than independent effects of carbohydrate restriction, total fat, or fat source.