Abstract Allogeneic stem cell transplantation (allo-HSCT) cures pediatric blood disorders, but graft-versus-host disease (GVHD) remains a major complication. This study investigated the link between gut microbiota and GVHD in 118 pediatric allo-HSCT patients (2020-2023). Fecal samples were collected pre-transplant and up to 90 days post-transplant.Patients developing GVHD (GVHD+, n=49) showed significantly reduced gut microbial diversity (α-diversity), especially at day 14, compared to non-GVHD patients (GVHD-, n=69). While initial community structure (β-diversity) was similar, GVHD+ patients had increased pro-inflammatory Proteobacteria and Actinobacteria, whereas GVHD- patients had more protective Stenotrophomonas. Machine learning identified predictive microbial features.Longitudinally, responders showed recovery of beneficial short-chain fatty acid (SCFA)-producing bacteria. Non-responders had persistent enrichment of Firmicutes and opportunistic pathogens. Functional analysis linked dysbiosis to impaired SCFA synthesis and carbohydrate metabolism.The findings highlight the gut microbiota's dual role as both a biomarker and modulator of acute GVHD. Strategies preserving microbial diversity, restoring SCFA producers, and using predictive microbial models could improve clinical outcomes, underscoring the potential for microbiota-targeted interventions to reduce GVHD and enhance transplant success.
Jiang et al. (Mon,) studied this question.
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