Gut microbiome crosstalk in acute myeloid leukemia: mechanisms, treatment-associated dysbiosis, and translational opportunities.

Acute myeloid leukemia (AML) is accompanied by perturbations of the intestinal microbiome, but causal relationships remain incompletely defined because most patient data are cross-sectional and confounded by age, diet, antibiotic exposure, hospitalization, neutropenia, and chemotherapy. This review evaluates current evidence for AML-microbiome crosstalk, considering patient microbiome/metabolome associations; AML mouse and cell models; treatment-induced dysbiosis during induction chemotherapy and antimicrobial exposure; and microbiome-targeted interventions. The strongest AML-specific mechanistic evidence implicates intestinal barrier injury, microbial translocation/lipopolysaccharide (LPS) signaling, depletion of short-chain fatty acid (SCFA)-producing bacteria, altered propionate and butyrate availability, and bile-acid remodeling, including preclinical AML-inhibitory activity of chenodeoxycholic acid. Evidence for indoles, hydrogen sulfide, serotonin, precision probiotics, dietary interventions, time-restricted feeding, methionine restriction, and curcumin is more preliminary or extrapolated from non-AML cancer models. Fecal microbiota transplantation restores microbial diversity after induction therapy in early clinical trials, but infection-prevention and survival benefits remain unproven, and safety is a central concern in neutropenic and hematopoietic stem cell transplantation (HSCT) patients. We describe mechanistic gaps and propose a translational scheme that recommends longitudinal sampling, compartment-specific metabolite measurements, antimicrobial surveillance, and trial designs that distinguish microbiome restoration from clinical efficacy.