Host-microbe interactions and outcomes in multiple myeloma and hematopoietic stem cell transplantation

Abstract

Microbiota are essential to normal immune development and there is growing recognition of its importance to human health and disease and deepening understanding of the complexity of host-microbe interactions in the human gut and other tissues. Commensal microbes not only can influence host immunity locally through impacts of bioactive microbial metabolites and direct interactions with epithelial cells and innate immune receptors but also can exert systemic immunomodulatory effects via impacts on host immune cells capable of trafficking beyond the gut. Emerging data suggest microbiota influence the development of multiple myeloma (MM), a malignancy of the immune system derived from immunoglobulin-producing bone marrow plasma cells, through the promotion of inflammation. Superior treatment outcomes for MM correlate with a higher abundance of commensal microbiota capable of influencing inflammatory responses through the production of butyrate. In patients with hematologic malignancies, higher levels of diversity of the gut microbiota correlate with superior outcomes after hematopoietic stem cell transplantation. Correlative data support the impact of commensal microbiota on survival, risk of infection, disease relapse, and graft-versus-host disease (GVHD) after transplant. In this review, we will discuss the current understanding of the role of host-microbe interactions and the inflammatory tumor microenvironment of multiple myeloma, discuss data describing the key role of microbiota in hematopoietic stem cell transplantation for treatment of hematologic malignancies, and highlight several possible concepts for interventions directed at the gut microbiota to influence treatment outcomes.