{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:09:39Z","timestamp":1788869379090,"version":"build-2803163510"},"reference-count":98,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"In-house Talent Training Project of the Affiliated Hospital of Gansu University of Chinese Medicine","award":["070005583"],"award-info":[{"award-number":["070005583"]}]},{"name":"Preclinical Study of Innovative Traditional Chinese Medicine Yangbing Plaster Hydrogel for the Treatment of Knee Synovitis","award":["2026CYZC-053"],"award-info":[{"award-number":["2026CYZC-053"]}]},{"name":"Gansu Province University Industry Support Project"},{"name":"National Traditional Chinese Medicine Key Specialty Construction Project\u2013Orthopedics and Traumatology"},{"name":"Inheritance Studio of Chief TCM Doctor Li Ning, Gansu Province"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Osteoporosis is one of the most prevalent metabolic bone diseases worldwide, and current pharmacological options are limited by adverse effects and are poorly suited to long-term use, underscoring the need for novel therapeutic targets. Bifidobacterium, one of the most representative beneficial bacterial genera in the human gut, has been linked to bone mineral density, and supplementation with specific strains improves bone metabolic parameters in animal models of osteoporosis. This narrative review examines the molecular mechanisms through which Bifidobacterium may protect bone via the gut\u2013bone axis, encompassing four interconnected dimensions: reinforcement of the intestinal barrier, modulation of the immune network, remodeling of the gut microbiota, and production of bone-protective metabolites. The review makes three principal contributions. First, it establishes a four-tier mechanistic framework of Bifidobacterium-mediated regulation of osteoporosis in which the evidence is stratified into three categories\u2014direct evidence from Bifidobacterium-specific studies, indirect evidence from other probiotics, and general mechanisms of gut microbiota-regulated bone metabolism\u2014thereby strengthening the rigor of each argument and explicitly distinguishing evidence derived from Bifidobacterium-specific studies from that based on other probiotics or general gut-microbiota mechanisms throughout the review. Second, it systematically compares the osteoprotective efficacy of different Bifidobacterium strains (Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium adolescentis, etc.), highlighting the central importance of strain specificity. Third, it evaluates the strength of the evidence and identifies knowledge gaps for each mechanistic pathway. Most current evidence derives from cross-sectional studies and animal models; causal relationships await validation in large-scale prospective cohort studies and randomized controlled trials. In addition, functional disparities among strains and heterogeneity across clinical studies remain the core bottleneck in translating these fundamental findings into clinical practice.<\/jats:p>","DOI":"10.3390\/microorganisms14091985","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:23:51Z","timestamp":1788866631000},"page":"1985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intestinal\u2013Bone Axis Mediated by Bifidobacterium: Mechanistic Analysis and Therapeutic Potential in Osteoporosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Fadong","family":"Li","sequence":"first","affiliation":[{"name":"School of Clinical Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoze","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Clinical Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boran","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Clinical Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwen","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Clinical Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730013, China"},{"name":"Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"School of Clinical Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730013, China"},{"name":"Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00198-025-07422-3","article-title":"Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: A consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)","volume":"36","author":"Bhattoa","year":"2025","journal-title":"Osteoporos. 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