Hematopoietic stem cell transplantation disrupts age-related gut microbiota signatures in pediatric and adult recipients

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) profoundly reshapes the gut microbiome (GM), yet age-related differences in this process remain incompletely understood. In this study, we analyzed stool samples from a cohort of pediatric and adult patients collected before allo-HSCT and at neutrophil engraftment to assess GM dynamics. We observed a significant reduction in alpha diversity post-HSCT across both age groups, with young patients displaying notably lower biodiversity. While GM composition varies among age ranges before transplantation, these distinctions largely disappeared at neutrophil engraftment, indicating a convergence toward a more uniform “transplant-specific” signature. This shift entailed a loss of health-associated, butyrate-producing taxa and a rise in potentially opportunistic bacteria (e.g., Enterococcaceae, Staphylococcaceae). Low pre-allo-HSCT GM diversity correlated with an increased risk of clinically significant acute graft-versus-host disease, overwhelming the age differences, underscoring the clinical relevance of maintaining a balanced microbiome before transplantation. Overall, our findings highlight the importance of age in shaping the pre-transplant GM and reveal how allo-HSCT-driven factors homogenize microbial communities among age ranges, offering insights for future microbiome-targeted interventions to improve transplant outcomes.