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 and 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. 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. A larger change in alpha diversity between the pre-CLL engraftment (F1) and 4-weeks post-engraftment (F3) assessment significantly correlated with higher disease burden at week 4 ( Discussion: Collectively our data provides evidence of the profound and sustained impact of a high-fat Western diet on the gut microbiome community and CLL pathogenesis in the Eµ-TCL1 murine model of CLL.