{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:01:34Z","timestamp":1785391294296,"version":"3.55.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Degenerative musculoskeletal and metabolic bone diseases are increasingly recognized as conditions sustained not only by endocrine and mechanical factors, but also by chronic low-grade immune activation and osteo-immune imbalance. This Perspective proposes a mechanistic framework in which gut dysbiosis may contribute to skeletal degeneration through alterations in vitamin-dependent immune regulation, with particular attention to the interaction between vitamin D signaling and microbiota-derived menaquinones. Dysbiosis may impair intestinal barrier integrity and increase exposure to microbial-associated molecular patterns, thereby sustaining innate and adaptive immune activation and promoting a pro-inflammatory cytokine milieu involving IL-6, TNF-\u03b1, IL-17, and IL-1\u03b2. These pathways may promote osteoclastogenesis and disrupt bone remodeling through the RANKL\/RANK\/OPG axis. While the immunomodulatory role of vitamin D is well established, microbiota-derived menaquinones may represent a less explored but biologically plausible interface between microbial metabolism, inflammatory signaling, and skeletal homeostasis . However, the extent to which microbiota-derived menaquinones significantly contribute to systemic vitamin K status in humans remains controversial and incompletely characterized. Within this framework, dietary patterns are conceptualized as modulators of microbial ecology and immune activation, while microbiota-modulating strategies may indirectly influence osteo-immune balance through immune-mediated mechanisms. This Perspective integrates microbial, immunological, and vitamin-dependent pathways into an immunology-centered model of skeletal degeneration and highlights the need for studies combining microbiome profiling, immune phenotyping, vitamin-dependent signaling, and bone remodeling outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1920962","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:38:30Z","timestamp":1785389910000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut dysbiosis and vitamin-dependent immune regulation in degenerative musculoskeletal and bone diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Nicola","family":"Stefanelli","sequence":"first","affiliation":[{"name":"Independent Researcher","place":["Montecatini Terme, 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