Acute myeloid leukemia and gut microbiome: bidirectional effects and opportunities for intervention.

Acute myeloid leukaemia (AML) is characterized by substantial treatment-related morbidity that is not fully explained by cytogenetic or molecular risk stratification alone. Emerging evidence implicates the gut microbiome as a critical, modifiable determinant of AML pathogenesis, therapeutic response, and treatment-related complications. Patients with AML exhibit profound gut microbiome disruption at diagnosis, marked by reduced microbial diversity and depletion of short-chain fatty acid-producing commensals, which is further exacerbated by intensive chemotherapy, antibiotic exposure, and hematopoietic stem cell transplantation (HSCT). These perturbations impair intestinal barrier integrity, amplify systemic inflammation, and promote domination by opportunistic and multidrug-resistant organisms, thereby increasing the risks of mucositis, bloodstream infections, graft-versus-host disease, and mortality. Beyond complications, microbiome-derived metabolites modulate immune signalling, hematopoietic homeostasis, and inflammatory pathways relevant to clonal haematopoiesis and leukemogenesis, suggesting bidirectional interactions between the microbiome and AML biology. Observational and translational studies demonstrate that preserved microbial diversity and enrichment of specific taxa are associated with improved survival following HSCT, while dysbiosis correlates with inferior outcomes. Interventions aimed at microbiome preservation and restoration-including antibiotic stewardship, dietary modulation, autologous or donor fecal microbiota transplantation, and emerging postbiotic strategies-have shown feasibility and biologic efficacy, although definitive clinical benefit remains to be established. This review synthesizes current mechanistic, clinical, and translational evidence linking gut microbiome dysregulation with AML outcomes, highlights emerging therapeutic strategies, and outlines key challenges and future directions. Integrating microbiome-focused supportive care into AML management represents a promising avenue to reduce treatment toxicity and improve patient outcomes.