Data from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia

<div>Abstract<p>The gut microbiome’s role in the pathogenesis of hematologic malignancies is actively being explored; yet studies on chronic lymphocytic leukemia (CLL) are limited. Using the Eμ-TCL1 murine model of CLL, we identify a unique and dysbiotic disease-associated gut microbiome that develops in mice over time. Leukemic mice show an increase in abundance of pathogenic bacteria, specifically members of the <i>Proteobacteria</i> phylum. We found that this dysbiotic microenvironment is associated with CLL involvement within the intestinal tract and high levels of markers indicative of altered tight junction permeability (e.g., claudin-2, soluble CD14, and zonulin). Moreover, utilizing the syngeneic model of CLL in tandem with an antibiotic-mediated microflora ablation approach, we found that leukemic mice receiving microflora-ablating antibiotics show marked changes to the gut microbiome and a delayed disease onset compared with mice receiving antibiotic-free water. Immunophenotyping of murine spleens showed that this delay in disease was accompanied by more tumor-reactive CD8<sup>+</sup> T cells that coexpressed fewer inhibitory receptors (e.g., PD-1, LAG-3, and TIM-3). These findings confirm that a dysbiotic gut microbiome develops during CLL disease and demonstrate unique intestinal involvement and potential immune dysregulation occurring during CLL progression that may be influencing the overall microbial signature.</p>Significance:<p>There is a growing appreciation for the gut microbiome’s role in hematologic malignancies. Despite this, its role in CLL remains obscure. This study demonstrates a dysbiotic microbiome within CLL that may contribute to further intestinal and immune dysregulation present during CLL progression.</p></div>