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Recent studies suggest that factors such as bicarbonate and gut microbiota may play key roles in bone health. Mineral water, rich in bicarbonate, may influence bone health and the gut\u2013bone axis under such conditions. Methods: Mice were exposed to hypoxia and treated with different concentrations of drinking water. Bone-related parameters were assessed using dual-energy X-ray absorptiometry (DXA) and Micro-CT. Bone health was assessed using the measurement of serum biomarkers. Additionally, Untargeted Metabolomics was employed to analyze differential metabolites between groups, while gut microbiota composition was analyzed using 16S rRNA sequencing. Results: BMW consumption increased bone mineral density (BMD) and helped alleviate the damage to the microstructure of bones caused by hypoxia and delayed the progression of osteoporosis. Additionally, BMW was shown to enhance probiotics such as Akkermansia and Dubosiella and regulate the longevity-regulating pathway as well as the PI3K\/AKT\/mTOR (PAM) signaling pathway. This study also discovered changes in metabolic products due to BMW intervention, predominantly in pathways such as the amino acid, prostaglandin, and purine metabolisms, with correlation analysis further exploring the relationships between gut microbiota and these differential metabolites. Conclusions: Long-term exposure to high-altitude hypoxic conditions affects the structure of gut microbiota and bone metabolism in mice. The consumption of BMW improves the structure of gut microbiota and regulates the metabolic pathways to maintain bone health under high-altitude hypoxia.<\/jats:p>","DOI":"10.3390\/nu17060998","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:31:42Z","timestamp":1741764702000},"page":"998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bicarbonate-Rich Mineral Water Mitigates Hypoxia-Induced Osteoporosis in Mice via Gut Microbiota and Metabolic Pathway Regulation"],"prefix":"10.3390","volume":"17","author":[{"given":"Yufan","family":"Ding","sequence":"first","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Liu","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xue","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Yang","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8028-6691","authenticated-orcid":false,"given":"Chenyu","family":"Li","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang","family":"Wang","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1199-3397","authenticated-orcid":false,"given":"Zhigang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Shen","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2005). 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