Gut microbiota dysbiosis in pediatric acute lymphoblastic leukemia: clinical consequences, mechanistic insights, and microbiota-targeted interventions.

Gut microbiota dysbiosis has emerged as a key feature in pediatric acute lymphoblastic leukemia (ALL), driven by chemotherapy, antibiotic exposure, and treatment-related nutritional impairment. Increasing evidence indicates that disruption of microbial diversity and depletion of short-chain fatty acid-producing bacteria are closely associated with infectious complications, gastrointestinal toxicity, and potentially reduced treatment efficacy. This review synthesizes current evidence on the interplay between gut microbiota and pediatric ALL across four dimensions: clinical outcomes, treatment-related toxicity, pharmacological interactions, and prognosis. We further summarize how leukemia therapy reshapes microbial ecosystems through cytotoxic agents, antimicrobial exposure, and dietary alterations. In addition, we discuss microbiota-centered therapeutic strategies, including probiotics, prebiotics, synbiotics, postbiotics, dietary interventions, and fecal microbiota transplantation. While promising, these approaches require careful validation in pediatric oncology due to safety considerations and limited clinical trial data. Finally, we highlight methodological advances such as multi-omics integration and machine learning approaches, which may enable microbiome-based risk stratification and precision supportive care in the future. Overall, gut microbiota represents a potential modifiable factor influencing clinical outcomes in pediatric ALL.