{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:09:33Z","timestamp":1788930573881,"version":"build-2803163510"},"reference-count":152,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Fund for High-end Talents of Shenzhen","award":["000700"],"award-info":[{"award-number":["000700"]}]},{"name":"Stability Support Program of Shenzhen Universities and Colleges","award":["20231122174953002"],"award-info":[{"award-number":["20231122174953002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The gut microbiota can influence tumor immunity and treatment responses through microbial metabolism, intestinal barrier regulation, and immune\u2013inflammatory signaling, but whether exercise engages these mechanisms through the muscle\u2013gut axis remains uncertain. This review integrates evidence from exercise physiology, microbial metabolism, and tumor immunology to examine how exercise-associated host signals may reshape the intestinal ecological niche and microbial function. Three candidate muscle\u2013gut axes are proposed: the myokine\u2013enteroendocrine\u2013substrate delivery\u2013short-chain fatty acid (SCFA) axis, the exercise-associated lactate\u2013microbial cross-feeding\u2013propionate axis, and the muscle-derived endocrine signaling\u2013intestinal epithelial repair\u2013hypoxic niche axis. Separate studies support exercise-associated IL-6\/GLP-1\/PYY regulation and gastrointestinal transit, lactate entry into the intestinal lumen and lactate-associated microbial remodeling, Veillonella atypica-mediated propionate production, and irisin\/apelin-related epithelial repair. Together, these pathways may influence microbial metabolism, barrier homeostasis, and immune\u2013tumor interactions. However, tumor-related links remain incomplete, and none has been validated as a complete causal chain in a single tumor-bearing exercise model. Relatively complete preclinical evidence comes from mouse melanoma, where endurance exercise enhanced microbial folate-dependent one-carbon metabolism and formate output, with microbiota-derived formate promoting CD8+ T-cell antitumor activity and immune checkpoint inhibitor efficacy. Regular exercise with an appropriate load and adequate recovery may support microbial and intestinal barrier homeostasis, whereas excessive or prolonged exercise with inadequate recovery may impair barrier integrity. Human evidence remains limited and largely associative and does not establish microbiota-mediated improvements in tumor immunity or treatment responses. These candidate axes therefore require causal validation in tumor-bearing exercise models and prospective human studies.<\/jats:p>","DOI":"10.3390\/metabo16090638","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:43Z","timestamp":1788275323000},"page":"638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Exercise-Mediated Regulation of the Gut Microbiota via the Muscle\u2013Gut Axis: Implications for Tumor Immunity and Treatment Responses"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3919-9989","authenticated-orcid":false,"given":"Tao","family":"Pang","sequence":"first","affiliation":[{"name":"School of Sports, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Sports, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Sports, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41522-025-00678-x","article-title":"Gut microbiota as a new target for anticancer therapy: From mechanism to means of regulation","volume":"11","author":"Sun","year":"2025","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev-pharmtox-061124-102218","article-title":"Gut microbiota\u2013related biomarkers in immuno-oncology","volume":"65","author":"Silva","year":"2025","journal-title":"Annu. 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