From dysbiosis to precision supportive care: the gut microbiota-immune axis in pediatric acute lymphoblastic leukemia

Long-term survival in pediatric acute lymphoblastic leukemia (ALL) exceeds 90% in high-income countries, yet life-threatening infections, chemotherapy-induced mucositis, and impaired hematopoietic recovery remain major challenges. The gut microbiota-immune axis offers a framework for investigating these complications, but its contribution in pediatric ALL remains uncertain. This critical review distinguishes direct pediatric ALL observations from pediatric transplantation evidence and external mechanistic studies. A structured revision-stage search retained 156 clinical reports for design-specific appraisal. We examine intestinal barrier injury, innate immune signaling, regulatory T-cell (Treg)/T helper 17-cell (Th17) regulation, microbial metabolites, and associations with hematopoietic recovery without assuming causality in affected children. Pediatric studies associate microbial features with infection-related outcomes and neutrophil recovery; adult transplantation and chimeric antigen receptor T-cell (CAR-T) findings remain indirect. Small cohorts, heterogeneous sampling and sequencing, age-dependent microbiome maturation, and treatment-related confounding limit interpretation. Proposed priorities include longitudinal ALL cohorts, paired microbial and host measurements, independent biomarker validation, and safety-focused evaluation of antimicrobial and microbiota-targeted interventions. Microbiome associations alone do not justify changes to supportive care.