The Human Microbiome in Hematologic Malignancies

The significant role of gut microbiome in human physiology, immune modification and nutrients supply has been recognized and is advancing. Scientific reports suggest association of the human microbiome with the risk of various diseases including hematologic malignancies. Metabolites (such as short chain fatty acids (SCFAs)) released into the gut as a result of bacterial fermentation can enter the circulation and change the systemic metabolome. This can influence hematopoiesis and the nature of cells recruited to sites of inflammation. Bacterial metabolites especially SCFAs have an important role in host metabolism and serve to modulate immune responses. They have potential to activate several G Protein-Coupled Receptors (GPCRs) expressed on various immune cells. SCFAs have been shown to suppress nuclear factor Kappa B (NFkB) and inflammatory cytokines like IL-6 and tumor necrosis factor α (TNF-α) and they can also induce IL-10 production consequently affecting the generation of Th1 and Th17 cells and drive proliferation of T cells and B cells. The intimate, bidirectional relationship between microbes and host immune responses suggests the association of the microbiome with lymphoma and blood cancer. The role of pathogenic organisms such as Borrelia burgdorferi, Chlamydophila psittaci, Epstein-Barr virus (EBV), hepatitis C virus (HCV), Helicobacter pylori and human immunodeficiency virus (HIV) has been suggested to be associated with hematologic malignancies. Changes in the microbiome can result in excessive infection, tissue damage and pathology as well as in the development of hematologic malignancies and subsequently can have direct impact on overall patient outcome.