Gut microbiome and metabolome dynamics as predictors of clinical outcomes in hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) induces significant alterations in the gut microbiome and metabolome, which influence transplant-related complications and surviv-al. This study longitudinally analyzed gut microbiota and metabolites at pre- (T1), peri- (T2), and post-transplant (T3) stages to identify key determinants of clinical outcomes. Lower microbiome diversity at T1 and T3 correlated with graft-versus-host disease (GVHD), progressive disease (PD), and reduced overall survival (OS). Short-chain fatty acids (SCFAs), particularly acetate, declined over time, with reductions at T2-T1 linked to GVHD, diarrhea, PD, and lower OS. Specific perspective metabolites (SPMs) such as elevated uric acid at T2 were associated with GVHD, while reduced 1-phenylethylamine correlated with diarrhea. Patients with enriched beneficial taxa (e.g., Lachnospiraceae, Ruminococcaceae) exhibited improved OS. These findings highlight the gut microbiome-metabolome axis as a predictive marker for HSCT outcomes. Identifying microbial and metabolic signatures may provide novel diagnostic and therapeutic targets for mitigating HSCT-related complications, enhancing patient prognosis.