Using Linoleic Acid to Target Insulin Resistance and Prevent Muscle Atrophy in a Mouse Model of Cancer Cachexia

Objectives: Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer, often treated with intensive chemotherapy and antibiotic protocols that disrupt gut microbiota diversity and function.These disruptions can persist for years after treatment, leading to long-term health complications, including reduced microbial diversity, metabolic imbalances, and decreased physical fitness.This study investigated the impact of physical exercise and probiotic supplementation on gut microbiota, physical fitness, and overall health in pediatric patients with ALL in remission.Methods: This crossover study included 22 pediatric patients with ALL in remission (3-5 years post-treatment).Thirteen participants began as the experimental group and nine as the control group.The intervention consisted of an 8-week strength training program (3 sessions/week), followed by an 8-week intervention with daily consumption of probiotic dairy product containing Lactobacillus casei CNCMI-1518.Physical fitness and anthropometric measures were assessed alongside gut microbiota analysis using 16S rRNA sequencing.Results: Logistic regression analysis identified several variables significantly associated with probiotic intervention outcomes, identifying key predictors of gut microbiota improvements.The probiotic intervention increased gut microbiota diversity (Chao1 index, p0.065) and beneficial taxa, including butyrate producers Blautia caecimuris (p0.007) and Blautia schinkii (p0.024), as well as Lacticaseibacillus casei (p0.011) and Veillonellaceae (p0.054).Physical exercise showed a modest effect on the shift in gut microbiome; however, weight (p0.008) and BMI percentile (p0.023)improved in the experimental group, while no significant changes were observed in handgrip strength or jump performance.Conclusions: This study demonstrated that probiotic supplementation significantly improved gut microbiota diversity and increased beneficial taxa.Physical exercise did not influence gut microbiota composition but led to significant improvements in weight and BMI percentile in pediatric patients with ALL.These findings suggest that probiotics can effectively restore gut health, while exercise supports anthropometric recovery in this population.