Disease-specific gut microbiota-metabolite-immune networks in hematologic disorders: mechanisms, causal support, and translational strategies

The gut microbiota is increasingly recognized as a systemic regulator of host immunity, host metabolism, epithelial barrier integrity, and distal tissue homeostasis. Hematologic disorders provide an important setting in which these host-microbe interactions converge on immune remodeling, marrow-niche function, hematopoietic recovery, treatment response, and transplant-related complications. This narrative review synthesizes mechanistic, clinical, and translational evidence linking gut microbial dysbiosis to benign and malignant hematologic diseases, clonal and premalignant states, and hematopoietic stem cell transplantation (HSCT)-related outcomes. Rather than treating microbiome associations as a single evidence category, we distinguish five complementary evidence strata: Mendelian randomization, experimental models, prospective human cohorts, randomized human interventions, and cross-sectional studies. These study designs address different causal questions and are interpreted as complementary rather than as a single linear hierarchy. We also separate microbial composition from microbial function: taxon-level enrichment or depletion is treated primarily as context-dependent and hypothesis-generating, whereas conserved functional pathways-including short-chain fatty acids, bile-acid transformation, tryptophan metabolism, microbial translocation and barrier dysfunction, and innate immune activation-provide the principal cross-disease mechanistic framework. We integrate disease-specific microbial features, functional mediators, immune and marrow consequences, and clinical outcomes into an author-constructed evidence map, while explicitly addressing bidirectionality, reverse causality, and translational readiness. Emerging applications include microbiota-based biomarkers, treatment-response prediction, fecal microbiota transplantation, probiotics and postbiotics, antibiotic stewardship, and microbiota-dependent modulation of drug metabolism.