From dysbiosis to precision supportive care: the gut microbiota-immune axis in pediatric acute lymphoblastic leukemia.
This critical review appraises 156 clinical reports and concludes that gut microbial features are associated with infection-related outcomes and neutrophil recovery in pediatric ALL, while emphasizing substantial confounding, methodological heterogeneity, and lack of causal evidence.
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This critical review appraises 156 clinical reports and concludes that gut microbial features are associated with infection-related outcomes and neutrophil recovery in pediatric ALL, while emphasizing substantial confounding, methodological heterogeneity, and lack of causal evidence.
Research significance
Evidence summarized in the review links microbiome features with infections and hematopoietic recovery in pediatric ALL; as an unproven inference, validated microbiome-host biomarkers could eventually guide antibiotic stewardship or safety-focused microbiota-directed supportive care, but the record does not support changing current practice.
Source abstract
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.