REVIEW article
Front. Psychol.
Sec. Movement Science
This article is part of the Research TopicHarnessing Physical Activity for Cognitive Enhancement and Mental Health PromotionView all 10 articles
The Neuro-Immuno-Metabolic Axis of Exercise: A Unified Mechanistic Framework for Exercise-Induced Cognitive Enhancement and Psychological Resilience
Provisionally accepted
- Harbin Sport University, Harbin, China
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Background: Physical exercise is widely recognized for promoting cognitive function and psychological resilience; however, the precise systemic mechanisms remain fragmented across isolated disciplines. Existing models often fail to capture the complex, multi-systemic nature of these adaptations. Methods: We conducted a comprehensive literature search in PubMed, Web of Science, and Scopus databases up to December 2025. Keywords included “exercise,” “neuroinflammation,” “metabolism,” “kynurenine pathway,” and “gut-brain axis.” We prioritized high-quality preclinical and clinical studies that examined bidirectional cross-talk between at least two physiological systems (neural, immune, or metabolic) to construct a unified theoretical synthesis. Results: Based on this synthesis, we propose the “Neuro-Immuno-Metabolic (NIM) Axis.” Unlike linear bipartite models, this framework positions exercise as a systemic “energy challenge” that triggers a coordinated recalibration. Key mechanisms identified include: (1) Metabolic Signaling: Lactate, ketone bodies, and the PGC-1α-mediated kynurenine detoxification pathway act as systemic signalers; (2) Immune Regulation: Exercise drives a shift from pro-inflammatory surveillance to “repair-oriented inflammation” rather than binary M1/M2 phenotypes; and (3) Gut-Brain Integration: Gut metabolites (e.g., indoles, SCFAs) regulate central immune tolerance via AhR signaling. Furthermore, we delineate the mechanistic specificity of aerobic, resistance, and high-intensity interval training (HIIT). Conclusion: The NIM axis provides a novel, integrative framework that explains how metabolic stress is transduced into psychological resilience. These insights establish a theoretical foundation for precision exercise medicine and advocate for future multi-omics research to develop individualized interventions.
Keywords: cognitive enhancement, Exercise, Exercise Modality Specificity, gut-brain axis, Neuro-Immuno-Metabolic Axis, precision exercise medicine, PsychologicalResilience, Repair-Oriented Inflammation
Received: 22 Dec 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Shen, Mao, Yang, Chen, Wang, Cheng, Zhu, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Junjie Liu
Li Li
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