Regulatory mechanisms of high-polyphenol dietary intervention on exercise-induced immunosuppression during high-intensity training periods in adolescent athletes: a systems biology analysis based on immune-metabolic pathways

BACKGROUND: Exercise‐induced immunosuppression poses significant health risks for adolescent athletes during intensive training. This study investigated whether high‐polyphenol dietary intervention could maintain immune homeostasis through immunometabolic reprogramming. METHODS: Eighty adolescent athletes (aged 15‐17) were randomized to receive either high‐polyphenol supplementation (1200 mg/day: quercetin, EGCG, resveratrol, curcumin) or placebo during a 12‐week high‐intensity training period. Multi‐omics profiling (transcriptomics, proteomics, metabolomics, microbiomics) was performed at baseline, weeks 4, 8, and 12. RESULTS: The high‐polyphenol group maintained CD4 + /CD8 + ratios above clinical thresholds (1.65 ± 0.29 vs. 1.38 ± 0.42, p < 0.001) at peak training. Regulatory T cells increased 17.2% while Th17 cells remained stable, yielding favorable Treg/Th17 ratios (3.09 ± 0.82 vs. 1.58 ± 0.54, p < 0.001). Multi‐omics integration revealed 1,847 differentially expressed genes converging on NF‐κB suppression, AMPK‐mTOR activation, and Nrf2‐mediated antioxidant responses. Gut microbiome analysis showed doubled butyrate‐producing bacteria and twofold increased short‐chain fatty acid production. Salivary IgA declined only 6.5% versus 29.3% in placebo (p < 0.001). CONCLUSIONS: High‐polyphenol dietary intervention effectively prevents exercise‐induced immunosuppression through coordinated immunometabolic reprogramming, establishing a practical strategy for maintaining immune resilience in adolescent athletes.