Abstract
INTRODUCTION: Treatment of pediatric acute lymphoblastic leukemia (ALL) induces persistent gut microbiota dysbiosis. However, microbiota-targeted interventions remain limited. This study evaluated the independent effects of physical exercise and probiotic supplementation on gut microbiota composition in pediatric ALL patients in remission for <5 years. METHODS: Thirty patients were randomized to an experimental group (8-week exercise followed by 8-week daily probiotic intake) or a non-intervention control group. Gut microbiota composition, stool metabolite profiles, anthropometric parameters, and physical strength outcomes were assessed. RESULTS: Physical exercise improved handgrip strength and supported anthropometric stability, with only modest effects on gut microbiota composition. In contrast, probiotic supplementation induced a significant shift in gut microbial community structure permutational multivariate analysis of variance (PERMANOVA, R (2) = 0.036, p = 0.041), accompanied by increases in lactic acid bacteria (LAB) and short-chain fatty acid (SCFA)-producing taxa. DISCUSSION: Overall, probiotic supplementation had a greater impact on gut microbiota composition than physical activity, inducing targeted shifts toward a more favorable microbial profile in this clinically vulnerable population.