{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:10:19Z","timestamp":1787987419070,"version":"build-2784847793"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: This study investigated the relationships among mitochondrial energy metabolism, immune function, and gut microbiota in mice under a fatigued state, providing preliminary evidence for future nutrition-related mechanistic and intervention studies. Methods: Mice were adaptively fed for 4 days and then randomly divided into a normal control group (NC) and a fatigue model group (NM). Immune organ indices, serum IgG levels, thigh muscle ATP content, mitochondrial respiratory chain complex I\u2013IV activities, and gut microbiota composition were assessed using enzyme-linked immunosorbent assay (ELISA), microplate assays, and 16S rRNA gene sequencing. Results: Compared with the NC, the NM showed a significantly reduced spleen index, serum IgG levels, mitochondrial respiratory chain complex I, III, and IV activities, along with reduced ATP content. Regarding gut microbiota, mice in the NM exhibited disordered intestinal villus arrangement, inflammatory cell infiltration in the crypts and muscular layers, and markedly reduced intestinal microbial activity as well as protease and sucrase activities. 16S rRNA sequencing revealed fewer ASVs in the NM, with enrichment of Lactobacillaceae, Limosilactobacillus, and Ligilactobacillus, whereas the NC was characterized by Borkfalkiaceae and Borkfalkia. Linear discriminant analysis effect size (LEfSe) analysis identified Lactobacillaceae, Firmicutes_D, and Lactobacillales as characteristic taxa of the NM. Kyoto Encyclopedia of Genes and Genomes (KEGG) prediction indicated that fatigue-associated microbial functions were mainly related to carbohydrate, amino acid, and lipid metabolism. Correlation and RDA analyses further suggested that alterations in gut microbiota structure were closely associated with mitochondrial energy-related indicators and immune-related parameters. Conclusions: Fatigue was associated with alterations in energy metabolism, immune function, and gut microecology in mice. The \u201cgut microbiota\u2013energy metabolism\u2013immunity\u201d framework may represent a potential association-based framework and provides biological information to support future nutrition-related intervention studies.<\/jats:p>","DOI":"10.3390\/nu18122031","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"2031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fatigue-Associated Alterations in Gut Microbiota, Mitochondrial Energy Metabolism, and Immune Function in Mice: Implications for Future Nutrition Studies"],"prefix":"10.3390","volume":"18","author":[{"given":"Menghui","family":"She","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"},{"name":"Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8288-4115","authenticated-orcid":false,"given":"Huiyi","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"},{"name":"Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"},{"name":"Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3193-073X","authenticated-orcid":false,"given":"Zhoujin","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"},{"name":"Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100266","DOI":"10.1016\/j.bbih.2021.100266","article-title":"Dissecting the fatigue experience: A scoping review of fatigue definitions, dimensions, and measures in non-oncologic medical conditions","volume":"15","author":"Billones","year":"2021","journal-title":"Brain Behav. 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