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Vitamin D3 is a potential modulator of the gut\u2013eye axis, but its role in inflammation-induced myopia remains unclear. This study investigated whether vitamin D3 supplementation attenuates myopia progression by regulating retinal inflammation, gut microbiota composition, and microbiota-derived metabolites in a TGF-\u03b22\u2013induced myopia model. Three-week-old Brown Norway rats received weekly periocular TGF-\u03b22 injections with or without daily oral vitamin D3, and myopia development was evaluated on days 1 and 21 by axial length and refractive error. Cecal contents were analyzed for \u03b1- and \u03b2-diversity and taxonomic differences, and day-21 serum underwent untargeted metabolomic profiling of microbiota-derived metabolites, including bile acids and imidazole derivatives; Spearman correlation linked microbial or metabolic alterations with myopia progression. TGF-\u03b22 induced axial elongation, myopic refractive shifts, and upregulated retinal pro-inflammatory cytokines (p-NF\u03baB, IL-1\u03b2, TNF-\u03b1), while vitamin D3 supplementation markedly attenuated myopia progression and retinal inflammation. Cecal \u03b1-diversity did not differ among control, vitamin D3, TGF-\u03b22, and TGF-\u03b22+vitamin D3 groups, but vitamin D3 significantly reshaped \u03b2-diversity and reduced the Firmicutes\/Bacteroidota ratio. Distinct metabolite profiles were observed, with the vitamin D3 group showing reduced hyodeoxycholic acid and elevated imidazole derivatives (imidazolepropionic and methylimidazoleacetic acids). Vitamin D3 supplementation attenuated myopia progression by reducing retinal inflammation and concurrently reshaping the gut microbiome and its metabolites compared to the control and myopic groups. These results underscore the potential of vitamin D3 to modulate the gut\u2013retina axis as a nutritional approach for mitigating myopia development.<\/jats:p>","DOI":"10.3390\/biom16070939","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D3 Reshapes Gut Microbiota and Metabolite Profiles in a Rat Model of Inflammation-Induced Myopia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-7013","authenticated-orcid":false,"given":"Yung-Lan","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300044, Taiwan"},{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-An","family":"Hsu","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Department of Chemistry, National Central University, Taoyuan 320317, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-Shyh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Beauty Science, National Taichung University of Science and Technology, Taichung 404336, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Chinese Medicine, Asia University Hospital, Taichung 413505, Taiwan"},{"name":"Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 413305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9099-3151","authenticated-orcid":false,"given":"Peng-Tai","family":"Tien","sequence":"additional","affiliation":[{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"},{"name":"School of Medicine, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie Jiin-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yen","family":"Wu","sequence":"additional","affiliation":[{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8060-192X","authenticated-orcid":false,"given":"Chun-Yu","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300044, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9525-3232","authenticated-orcid":false,"given":"Lei","family":"Wan","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Office of Research and Development, Asia University, Taichung 413305, Taiwan"},{"name":"Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40101-024-00354-7","article-title":"The influence of the environment and lifestyle on myopia","volume":"43","author":"Biswas","year":"2024","journal-title":"J. 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