Impact of high-fat Western diet on chronic lymphocytic leukemia disease progression and gut microbiome profile in Eμ-TCL1 mice

Background: The composition and function of the gut microbiome have been shown to contribute to both health and disease. One of the most powerful modulators of microbial composition and function is diet. Materials & Methods: Using the Eμ-TCL1 murine model of B-cell chronic lymphocytic leukemia (CLL), we assigned male and female mice to a high-fat, high-carbohydrate Western diet (HF) or standard chow (CH) diet. Results: Mice consuming a HF diet had significantly shorter survival than those consuming a CH diet, irrespective of sex, with female mice exhibiting particularly poor outcomes. We also observed a significant increase in splenic involvement by CLL in the HF diet-fed mice at time of sacrifice. Mice receiving the HF diet demonstrated immediate and profound effects on the gut microbiome, marked by reduced alpha diversity and significantly different community composition as measured by beta diversity. Notably, there was a sustained increase in Akkermansia muciniphila and Bacteroidetes thetaiotaomicron in HF diet-fed mice, coupled with a corresponding increase in microbiome functional pathways related to arginine and histidine biosynthesis, chitin degradation, and nucleotide biosynthesis. Discussion: Collectively our data provides evidence of the profound and sustained impact of a high-fat Western diet upon the gut microbiome community and CLL pathogenesis in the Eμ-TCL1 murine model of CLL.