Gut Microbiome-Immune Interactions During Pediatric Hematopoietic Cell Transplantation: From Conditioning to GvHD...

Hematopoietic stem cell transplantation (HCT) offers curative potential for children with high-risk hematologic malignancies. However, this treatment carries significant risks, particularly acute graft-versus-host disease (aGvHD), which affects 30%-60% of pediatric recipients and causes 15%-20% of post-transplant deaths. The gut microbiome has emerged as a critical factor in aGvHD development, yet pediatric microbiome dynamics differ substantially from adult patterns. This review seeks to evaluate the current state of knowledge of how the gut microbiome impacts aGvHD pathogenesis and the methods of microbiome modulation that may lead to aGvHD prevention and treatment. Children's microbiomes undergo more rapid compositional shifts and contain distinct bacterial compositions enriched in taxa like Bifidobacterium and Lactobacillus. During transplant, conditioning regimens and antibiotics cause dramatic microbiome disruption in children. This eliminates beneficial bacteria that normally maintain intestinal barrier integrity and produce immunomodulatory metabolites. Consequently, this disruption triggers inflammatory cascades through bacterial translocation, impaired immune education, and altered metabolite production. Unlike adults, where low diversity consistently predicts poor outcomes, pediatric studies show inconsistent diversity-outcome relationships, with only pre-transplant microbiome patterns reliably predicting aGvHD risk. Several promising interventions have emerged from this research. These include enteral nutrition to preserve beneficial bacteria, targeted antibiotic strategies, and fecal microbiota transplantation. Fecal microbiota transplantation has shown remarkable response rates in pediatric steroid-resistant aGvHD cases. Nevertheless, significant knowledge gaps remain regarding pediatric-specific mechanisms, optimal biomarkers, and age-appropriate therapeutic approaches for microbiome-directed aGvHD prevention.