Gut Microbiome Alterations in Aplastic Anemia: Mechanistic Insights, Immune-Hematopoietic Crosstalk and Therapeutic Potential

Aplastic anemia (AA) is a rare hematological disorder characterized by peripheral cytopenias and hypocellular bone marrow resulting from failed hematopoiesis. The condition may arise from inherited genetic defects in hematopoietic stem cells (HSCs) or from acquired immune-mediated mechanisms. In acquired AA, immune dysregulation leads to the destruction of hematopoietic stem and progenitor cells (HSPCs), with immunosuppressive therapy remaining the cornerstone of treatment. Emerging evidence highlights the gut microbiome as a critical modulator of immune function and hematopoiesis. Disruptions in gut microbial composition have been linked to autoimmune and inflammatory diseases, yet their specific role in AA pathogenesis is not fully understood. The gut microbiome may influence immune responses, hematopoietic recovery and disease progression. Profiling the gut microbiome could also serve as a non-invasive method for monitoring disease progression, identifying microbial patterns associated with treatment response and assessing individual risk for relapse. Despite these promising insights, clinical trials specifically targeting the gut microbiome in AA remain limited, revealing a significant gap in research. A deeper understanding of the interactions between the gut microbiome, immune system and hematopoiesis is essential for identifying novel biomarkers and therapeutic strategies. These insights could complement existing immunosuppressive therapies and enable more personalized treatment approaches. This review thus synthesizes current evidence on gut microbiome alterations in AA, exploring their potential role in immune regulation, hematopoietic recovery and therapeutic interventions.