Exploring the anti-central fatigue effects of tartary buckwheat polyphenols via the microbiota-gut-brain axis

Central fatigue is closely linked to disruptions in the microbiota-gut-brain axis (MGBA), yet the molecular mechanisms involved remain largely unclear, and effective nutritional interventions are still limited. Tartary buckwheat polyphenols (TBP) have demonstrated potential in modulating the gut microbiota and supporting neuronal function. However, the specific pathways through which TBP exert their anti-fatigue effects are not fully understood. Clarifying these mechanisms is crucial for the development of precision dietary strategies to alleviate central fatigue. In this work, we established a mouse model of overexercise-induced central fatigue to systematically evaluate the effects of TBP through behavioral assessments, histological examination, neurotransmitter profiling, and inflammatory and oxidative stress marker analysis. The results showed that TBP significantly improved fatigue-related behaviors, alleviated intestinal and brain tissue damage, and modulated the expression of various neurotransmitters. Furthermore, TBP significantly reduced serum levels of pro-inflammatory cytokines (e.g., interleukin-1 beta, and tumor necrosis factor-alpha), and mitigated oxidative stress by enhancing glutathione peroxidase and catalase activity and reducing malondialdehyde levels. 16S rRNA sequencing revealed that TBP altered gut microbiota composition, promoting the abundance of beneficial taxa such as Lachnospiraceae, Lactobacillus, and Roseburia, while suppressing potentially harmful microbes. Short-chain fatty acids analysis further demonstrated that TBP modulated levels of acetic, propionic, and butyric acids, contributing to intestinal barrier integrity and energy homeostasis. Metabolomics analysis revealed that TBP influenced several key pathways, including alanine, aspartate, and glutamate metabolism, as well as neuroactive ligand-receptor interactions, thereby restoring the metabolic balance under central fatigue. Collectively, this work provides supportive evidence that TBP alleviates central fatigue through modulating the MGBA.