The diversity of the microbiome impacts chronic lymphocytic leukemia development in mice and humans
Tereza Faitova,
Mariana Coelho,
Caspar da Cunha-Bang,
Selcen Ozturk,
Ece Kartal,
Peer Bork,
Martina Seiffert,
Carsten U. Niemann
Affiliations
Tereza Faitova
Department of Hematology, Rigshospitalet, Copenhagen
Mariana Coelho
Department of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Biosciences of the University of Heidelberg, Heidelberg
Caspar da Cunha-Bang
Department of Hematology, Rigshospitalet, Copenhagen
Selcen Ozturk
Department of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg
Ece Kartal
Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg
Peer Bork
Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; Department of Bioinformatics, Biocenter, University of Wurzburg, Wurzburg, Germany; Yonsei Frontier Lab (YFL), Yonsei University, Seoul, South Korea; Max Delbruck Center for Molecular Medicine, Berlin
Martina Seiffert
Department of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg
Carsten U. Niemann
Department of Hematology, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen
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. Stool sample analysis of 59 CLL patients revealed individual and heterogeneous microbiome compositions, but allowed for grouping of patients according to their microbiome diversity. Interestingly, CLL patients with a lower microbiome diversity and an enrichment of bacteria linked to poor health suffered from a more advanced or aggressive form of CLL. 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 diversity which was dominated by Mucispirillum and Parabacteroides genera in comparison to mice kept under lower hygiene conditions. In conclusion, we applied taxonomic microbiome analyses to demonstrate a link between the gut microbiome diversity and the clinical course of CLL in humans, as well as the development of CLL in mice. Our novel data serve as a basis for further investigations to decipher the pathological and mechanistic role of intestinal microbiota in CLL development.
