The role of the microbiota in hematological malignancies: A narrative review of mechanisms and therapeutic potential

The human microbiota, particularly the gut microbiome, plays a central role in maintaining immune homeostasis, regulating hematopoiesis, and modulating host metabolism through bioactive metabolites such as short-chain fatty acids (SCFAs), bile acids, and tryptophan-derived compounds. Disruption of this microbial ecosystem (dysbiosis) has emerged as a key contributor to the development and progression of hematological malignancies (HMs), including acute and chronic leukemias, lymphomas, and multiple myeloma. This narrative review synthesizes recent evidence (2022-2025) on the complex bidirectional interactions between the microbiota and HMs, highlighting their biological and clinical significance. Current evidence indicates that the microbiota influences hematological malignancies through multiple interconnected mechanisms, including immune regulation, inflammatory signaling, maintenance of hematopoietic homeostasis, and microbial metabolite-mediated modulation of the tumor microenvironment. Dysbiosis has been associated with disease progression, increased susceptibility to infections, impaired treatment tolerance, and inferior clinical outcomes. Conversely, chemotherapy, broad-spectrum antibiotics, and hematopoietic stem cell transplantation profoundly reshape microbial communities, further exacerbating dysbiosis and contributing to complications such as graft-versus-host disease following allogeneic transplantation. Emerging microbiota-targeted interventions, including dietary modulation, probiotics, prebiotics, and fecal microbiota transplantation, show promise for restoring microbial homeostasis and improving therapeutic outcomes. Furthermore, microbiome-derived biomarkers are increasingly being investigated for predicting treatment response, relapse risk, and immunotherapy efficacy. Despite these advances, important challenges remain, particularly in establishing causal relationships, standardizing microbiome profiling, and validating clinical applications through well-designed prospective and randomized studies. Overall, the accumulating evidence supports the microbiota as a critical determinant of hematological cancer biology and treatment response. Integrating microbiome-based diagnostics and therapeutic strategies into precision hematology may offer new opportunities to improve patient management and long-term clinical outcomes.