Prebiotic Modulation of the Gut-Muscle Axis and Moderate Exercise Performance: A Systematic Review and Meta-Analysis

Context: Emerging evidence suggests the “gut-muscle axis”—the interaction between gut microbiota and skeletal muscle—influences exercise performance, metabolic efficiency, and recovery. Prebiotics are nondigestible fibers that stimulate beneficial gut microbes to increase short-chain fatty acid (SCFA) production, potentially affecting host signaling and immune regulation during physical activity. Objective: This review synthesized current evidence regarding the effects of prebiotic supplementation on exercise performance and the mechanisms linking gut modulation to physiological adaptations. Design: Systematic review and meta-analysis of human randomized controlled trials (RCTs), with complementary narrative synthesis of mechanistic animal studies. Eligibility Criteria: Human RCTs and controlled animal experiments investigating defined prebiotics (e.g., inulin, β-glucans) and reporting on exercise performance, physiological responses, or microbiota alterations. Study Selection: PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to recent availability. From 1245 screened records, 42 full-text articles were assessed, yielding 15 included studies (8 human and 7 animal). Main Outcome Measures: Primary outcomes included maximal aerobic capacity ( ) and endurance performance. Secondary outcomes encompassed microbiota composition, SCFA production, and immune/inflammatory responses. Results: Meta-analysis of human RCTs revealed no significant improvements in or endurance performance (very low Grading of Recommendations Assessment, Development, and Evaluation certainty). However, submaximal efficiency in low-habitual-fiber consumers showed promise. Conversely, while animal models consistently demonstrated SCFA-driven endurance gains, associated with metabolic signaling activation and glycogen sparing, these specific effects remain to be reliably translated to human athletes. Furthermore, human trials showed prebiotics attenuated exercise-induced immunosuppression, preserved mucosal immunoglobulin A, and reduced respiratory infections. Conclusions: Current evidence does not demonstrate significant improvements in human or endurance performance from isolated prebiotic supplementation. However, prebiotics were associated with improved mucosal immunity and reduced respiratory infections during intensive training. The robust SCFA-mediated endurance gains seen in animal models highlight a translational gap, demonstrating that preclinical ergogenic efficacy is highly dependent on specific baseline microbiota.