Exercise physiology meets sports nutrition The flavonoid–gut–muscle axis and its implications for recovery and exercise adaptation
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Background: Dietary flavonoids undergo extensive host and microbial metabolism, producing circulating metabolites that differ from parent compounds and vary substantially between individuals. This variability may contribute to heterogeneous exercise responses, but the underlying causal sequence remains unproven. Objective: To examine whether variability in microbial flavonoid metabolism could explain interindividual differences in exercise recovery and adaptation. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 30 August 2026. Of 110 unique records, 35 were excluded and 75 retained after full-text assessment. One reviewer conducted study selection and extraction, followed by a second criterion-based verification pass. Five principal human studies were appraised using the 2018 Mixed Methods Appraisal Tool. Evidence was synthesised narratively because of substantial heterogeneity. Results: Thirteen primary studies informed at least one component of the proposed model, including five human studies and eight animal or cellular experiments. Only two human studies combined flavonoid or polyphenol supplementation with exercise, and neither demonstrated mediation by a defined microbial metabolite or assessed functional recovery or performance outcomes. Two additional exercise studies examined gastrointestinal or microbiome responses without flavonoid exposure, while one non-exercise study investigated microbial flavan-3-ol metabolism. No observational study directly tested the complete model. Confidence in generalisability was limited by small samples, restricted populations, incomplete reporting of blinding procedures, and the absence of integrated mediator and functional outcome measures. Conclusion: Individuals may differ in exercise responses because they generate distinct systemic exposures to microbial flavonoid metabolites. Current evidence supports the early metabolic steps of the proposed pathway, but not microbial mediation of recovery or adaptation.
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