Gut Microbiome and Metabolome Dynamics as Predictors of Clinical Outcomes in Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) profoundly disrupts the gut microbiome and metabolome, which in turn influence immune‐related complications and patient outcomes. To systematically characterize these perturbations, we performed a longitudinal analysis of fecal microbiota composition and metabolite profiles in HSCT recipients at three critical timepoints: pre‐transplant (T1), peri‐transplant (T2), and post‐transplant (T3). We observed that reduced microbial diversity at T1 and T3 was strongly associated with increased incidence of graft‐versus‐host disease (GVHD), progressive disease (PD), and decreased overall survival (OS). Metabolomic profiling revealed a significant decline in short‐chain fatty acids (SCFAs), particularly acetate, from T1 to T2, which correlated with adverse clinical outcomes including GVHD, diarrhea, PD, and lower OS. Elevated levels of uric acid at T2 were predictive of GVHD onset, while decreased 1‐phenylethylamine was linked to transplant‐associated diarrhea. Furthermore, enrichment of beneficial bacterial taxa such as Lachnospiraceae and Ruminococcaceae was associated with improved survival. Together, these findings highlight the gut microbiome–metabolome axis as a dynamic biomarker for HSCT prognosis. This integrated insight offers potential avenues for microbiota‐targeted diagnostics and interventions aimed at mitigating transplant‐related complications and improving patient survival.