The Diversity of the Microbiome Impacts Chronic Lymphocytic Leukemia Development in Mice and Humans

Abstract

Abstract The gut microbiota play a critical role in maintaining a healthy human body and their dysregulation is associated with various diseases. In this study, we investigated the influence of the gut microbiome diversity on chronic lymphocytic leukemia (CLL) development. In the Eµ-TCL1 mouse model of CLL, we observed a faster course of disease when mice were housed in high hygiene conditions. Shotgun DNA sequencing of fecal samples showed that this was associated with a lower microbiome complexity which was dominated by Mucispirillum and Parabacteroidesgenera in comparison to mice kept under lower hygiene conditions. Stool sample analysis of CLL patients revealed individual and heterogeneous microbiome compositions, but allowed for grouping of patients according to their microbiome complexity. Interestingly, CLL patients with a lower microbiome diversity and an enrichment of bacteria linked to poor health suffered from a more progressed or aggressive form of CLL. In conclusion, we applied taxonomic microbiome analyses to demonstrate a link between the gut microbiota diversity and CLL development in mice and humans. Our novel data serve as a basis for further investigations to decipher the pathological and mechanistic role of intestinal microbiota in CLL development.