Clinical effects and applications of the gut microbiome in hematologic malignancies

Abstract

The gut microbiome and its effects on host immunity have exciting implications for cancer prognosis and therapy. Examples in allogeneic hematopoietic stem cell transplantation (allo-SCT) demonstrate the role of the gut microbiome as a biomarker for clinical outcomes, and animal models demonstrate how microbiota manipulation may augment therapeutic responses. There are multiple mechanisms that gut microbiota may have in affecting distant tumor environments, including control of cytokine release, dendritic cell activation, and T-cell lymphocyte stimulation. Recently, there has been a marked interest in understanding interactions between host and microbiome in hematologic malignancies. This review summarizes the current understanding of the gut microbiome and its impact on leukemia, lymphoma, multiple myeloma, and allo-SCT and highlights several broad methods for targeting the gut microbiome in therapeutic trials.

Keywords: butyrate; gut microbiome; hematologic malignancies; review; translational research.

Figure 1:. Potential Mechanisms of Microbiota Targeted Therapies

Four main microbiota-directed therapies include prebiotics, probiotics, antibiotics, and fecal transplantation. Each has a direct effect on modulating gut microbiota. Prebiotics work by increasing abundance of key species (i.e., butyrate producers). Antibiotics may reduce deleterious microbial populations. Probiotics introduce/augment a specific species, and fecal transplantation replaces the microbiome with one representing the donor. Each of these changes may communicate with the host immune system via circulation of bacterial DNA, pathogen/damage associated molecular patterns, or metabolite production. These signals may stimulate APC’s like dendritic cells or macrophages, which in turn activate T cell populations to produce anti-tumor effects. APC: antigen-presenting cell.