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This exploratory study investigated the associations between chondroitin sulfate (CS) supplementation and body weight control in ovariectomized (OVX) rats, a preclinical model for postmenopausal physiology. CS supplementation was associated with significantly reduced body weight gain and preserved adipocyte morphology. CS-treated OVX rats exhibited decreased gut microbiota diversity, with reduced abundance of Photobacterium and Rhodococcus and increased abundance of Turicibacter. Metabolomic analysis revealed elevated levels of carbohydrates, fatty acids, and their conjugates, some of which correlated with body weight parameters. Bioinformatic analysis identified enriched KEGG pathways including tyrosine metabolism, glucosinolate biosynthesis and thiamine metabolism. Collectively, these findings provide preliminary correlational evidence in an OVX rat model supporting the potential of CS as a food supplement for body weight control, although causal relationships and clinical applicability warrant further investigation in postmenopausal populations.<\/jats:p>","DOI":"10.3390\/biom16081095","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chondroitin Sulfate Supplementation Is Associated with Body Weight Control in Ovariectomized Rats: A Multi-Omics Study of Gut Microbiota and Metabolite Profiles"],"prefix":"10.3390","volume":"16","author":[{"given":"Qingshan","family":"Shen","sequence":"first","affiliation":[{"name":"Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation, Nanyang Institute of Technology, Zhang Zhongjing College of Chinese Medicine, Changjiang Road 80, Nanyang 473004, China"},{"name":"School of Food and Health, Henan College of Classical Chinese Medicine, Hansheng Road 1222, Nanyang 473013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2588-5007","authenticated-orcid":false,"given":"Yanli","family":"Ma","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation, Nanyang Institute of Technology, Zhang Zhongjing College of Chinese Medicine, Changjiang Road 80, Nanyang 473004, China"},{"name":"School of Food and Health, Henan College of Classical Chinese Medicine, Hansheng Road 1222, Nanyang 473013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Man, W., Wang, S., and Yang, H. 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