Influence of gut microbiota on chronic lymphocytic leukemia development and aggressiveness

Chronic lymphocytic leukemia (CLL) is highly heterogeneous both clinically and biologically. Although genetic factors have been identified, several lines of evidence suggest a role for environmental factors in disease onset and progression. Diet is a recognized risk factor for various diseases, including cancer, with an established relationship to the composition of the gut microbiome. Taking advantage of the widely used Eμ-TCL1 transgenic model, we investigated the relationship between diet, the gut microbiota, and CLL development. We randomized a cohort of Eμ-TCL1 mice to receive a normal standard diet (N) (n = 15) or an experimental diet rich in low-complexity carbohydrates and lower in proteins and fibers (HC/LPF) (n = 16) and observed a progressive shift in microbiome composition in animals fed with the HC/LPF diet, accompanied by an acceleration of disease progression and shortened survival. These effects were associated with an increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes in mice fed with the HC/LPF diet. Our data suggest a close link between the HC/LPF diet and Oscillospira, Ruminococcus, Mucispirillum, AF12, and Rikenella genera, possibly affecting CLL development. The present work paves the way for detailed studies to be conducted in controlled cohorts of patients with CLL to elucidate the role of diet in disease incidence and evolution.