{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T02:18:40Z","timestamp":1794277120968,"version":"4.9.0"},"reference-count":93,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sigrid Juselius Foundation"},{"id":[{"id":"https:\/\/ror.org\/00ckakm23","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["JP23K08670"],"award-info":[{"award-number":["JP23K08670"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Murata Foundation"},{"name":"Turku Collegium for Science, Medicine and Technology"},{"name":"IT-CSC Finland","award":["#2004931"],"award-info":[{"award-number":["#2004931"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Osteoporosis arises from disrupted bone remodeling, and growing evidence shows that gut microbiota and their metabolites have a major influence on skeletal health through the gut-bone and gut\u2013brain\u2013bone axes. In this systematic review, we synthesize findings from 932 studies to identify key microbial taxa, metabolites, and signaling pathways that modulate osteoblast and osteoclast activities. Short-chain fatty acids (SCFA), tryptophan-derived metabolites, and \u03b2-D-glucuronidase-related estrogen regulation emerge as central microbial mechanisms affecting bone formation and resorption. By integrating these data with the Phylobone extracellular matrix proteins database, we highlight Osteopontin and Cathepsin K as important downstream mediators linking microbial signals to bone matrix turnover. Probiotic strains (particularly Lactobacillus rhamnosus GG and L. reuteri) show potential to improve bone health through metabolic, immune, and endocrine pathways. Together, these findings outline a mechanistic framework connecting gut function to skeletal biology and identify promising microbiome-based targets for osteoporosis interventions.<\/jats:p>","DOI":"10.3390\/life16060909","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:09:07Z","timestamp":1779970147000},"page":"909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Gut\u2013Bone Axis: A Systematic Review on the Potential Intervention Pathways for Bone Health"],"prefix":"10.3390","volume":"16","author":[{"given":"Tom\u00e1s","family":"Cant\u00f3n-Cordeiro","sequence":"first","affiliation":[{"name":"Medicity Research Laboratory, Faculty of Medicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-878X","authenticated-orcid":false,"given":"Saeka","family":"Shimochi","sequence":"additional","affiliation":[{"name":"Medicity Research Laboratory, Faculty of Medicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9042-6528","authenticated-orcid":false,"given":"Miho","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Medicity Research Laboratory, Faculty of Medicine, University of Turku, 20520 Turku, Finland"},{"name":"Department of Engineering, La Salle Campus Barcelona, University Ramon Llull, 08022 Barcelona, Catalonia, Spain"},{"name":"Laboratory for Biomaterials and Bioengineering, Institute of Science Tokyo, Chiyoda, Tokyo 101-0062, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0072-8726","authenticated-orcid":false,"given":"Pere","family":"Puigb\u00f2","sequence":"additional","affiliation":[{"name":"Department of Animal and Food Science, Faculty of Veterinary Medicine, Autonomous University of Barcelona, 08193 Bellaterra, Catalonia, Spain"},{"name":"Department of Biology, University of Turku, 20014 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1021\/acschemneuro.3c00127","article-title":"Gut Microbiome-Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders","volume":"14","author":"Sasso","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.alit.2025.01.004","article-title":"The gut-organ axis: Clinical aspects and immune mechanisms","volume":"74","author":"Fukasawa","year":"2025","journal-title":"Allergol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41392-025-02329-1","article-title":"Organ cross-talk: Molecular mechanisms, biological functions, and therapeutic interventions for diseases","volume":"11","author":"Che","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e28435","DOI":"10.1016\/j.heliyon.2024.e28435","article-title":"Microbiota metabolites in bone: Shaping health and Confronting disease","volume":"10","author":"Han","year":"2024","journal-title":"Heliyon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41413-023-00281-w","article-title":"Phylobone: A comprehensive database of bone extracellular matrix proteins in human and model organisms","volume":"11","author":"Nakamura","year":"2023","journal-title":"Bone Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s42003-025-09292-1","article-title":"Bone mechano-response is driven by locomotion transitions during vertebrate evolution","volume":"9","author":"Shimochi","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41413-025-00417-0","article-title":"Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling","volume":"13","author":"Li","year":"2025","journal-title":"Bone Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s40520-025-02973-1","article-title":"Advancing care: Optimizing osteoporosis treatment in the older and oldest old population","volume":"37","author":"Panait","year":"2025","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_9","first-page":"46","article-title":"An overview and management of osteoporosis","volume":"4","year":"2017","journal-title":"Eur. J. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Noh, J.-Y., Yang, Y., and Jung, H. (2020). Molecular mechanisms and emerging therapeutics for osteoporosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207623"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhu, M., Zhang, X., Zhang, J., Chen, J., and Liang, L. (2026). The gut-bone axis: Mechanisms through which oleic acid regulates bone metabolism and its potential in preventing and treating osteoporosis. Front. Nutr., 13.","DOI":"10.3389\/fnut.2026.1745125"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11914-015-0292-x","article-title":"Prebiotic and probiotic regulation of bone health: Role of the intestine and its microbiome","volume":"13","author":"McCabe","year":"2015","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chu, X., Xing, H., Chao, M., Xie, P., and Jiang, L. (2025). Gut microbiota modulation in osteoporosis: Probiotics, prebiotics, and natural compounds. Metabolites, 15.","DOI":"10.3390\/metabo15050301"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.34133\/research.1178","article-title":"Gut Microbiota Regulates Brain-Bone Axis to Influence Osteoporosis Pathogenesis and Treatment","volume":"9","author":"Shi","year":"2026","journal-title":"Research"},{"key":"ref_15","first-page":"1","article-title":"Targeting the gut-bone axis through exercise: A novel approach to osteoporosis prevention and treatment (Review)","volume":"57","author":"Wu","year":"2026","journal-title":"Int. J. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/jbmr.2308","article-title":"Thrombospondin-1 regulates bone homeostasis through effects on bone matrix integrity and nitric oxide signaling in osteoclasts","volume":"30","author":"Amend","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2307971","DOI":"10.1002\/advs.202307971","article-title":"The Brain-Gut-Bone Axis in Neurodegenerative Diseases: Insights, Challenges, and Future Prospects","volume":"11","author":"Li","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jare.2025.07.033","article-title":"Gut microbiota-mediated regulation of skeletal development: A review of mechanistic analysis and interventional strategies","volume":"82","author":"Liu","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cong, B., and Zhang, H. (2025). The effects of combined calcium and vitamin D supplementation on bone mineral density and fracture risk in postmenopausal women with osteoporosis: A systematic review and meta-analysis of randomized controlled trials. BMC Musculoskelet. Disord., 26.","DOI":"10.1186\/s12891-025-09089-7"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Han, H., Yan, H., and King, K.Y. (2021). Broad-Spectrum Antibiotics Deplete Bone Marrow Regulatory T Cells. Cells, 10.","DOI":"10.3390\/cells10020277"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Peng, Y., Zhong, Z., Huang, C., and Wang, W. (2023). The effects of popular diets on bone health in the past decade: A narrative review. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1287140"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Puigb\u00f2, P., Leino, L.I., Rainio, M.J., Saikkonen, K., Saloniemi, I., and Helander, M. (2022). Does glyphosate affect the human microbiota?. Life, 12.","DOI":"10.3390\/life12050707"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e36506","DOI":"10.1097\/MD.0000000000036506","article-title":"Association between urinary glyphosate exposure and bone mineral density in adults","volume":"102","author":"Wang","year":"2023","journal-title":"Medicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117201","DOI":"10.1007\/s11356-023-30388-w","article-title":"Potential roles of gut microbiota in metal mixture and bone mineral density and osteoporosis risk association: An epidemiologic study in Wuhan","volume":"30","author":"Zhang","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41413-023-00264-x","article-title":"Modulation of bone remodeling by the gut microbiota: A new therapy for osteoporosis","volume":"11","author":"Lyu","year":"2023","journal-title":"Bone Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1186\/s12964-025-02538-9","article-title":"The interplay of estrogen, gut microbiome, and bone immunity in osteoporosis","volume":"23","author":"Chen","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Xie, X., Liu, H., Wan, K., Li, J., and Qi, P. (2025). The gut microbiota in osteoporosis: Dual roles and therapeutic prospects. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1617459"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"10","author":"Page","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_29","first-page":"57","article-title":"Systematic reviews and meta-analyses","volume":"20","author":"Uman","year":"2011","journal-title":"J. Can. Acad. Child. Adolesc. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00394-017-1445-8","article-title":"Gut microbiota functions: Metabolism of nutrients and other food components","volume":"57","author":"Rowland","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115317","DOI":"10.1016\/j.bone.2020.115317","article-title":"The role of gut microbiota in bone homeostasis","volume":"135","author":"Behera","year":"2020","journal-title":"Bone"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1302\/2046-3758.101.BJR-2020-0273.R1","article-title":"The role of gut microbiota in bone homeostasis","volume":"10","author":"Li","year":"2021","journal-title":"Bone Jt. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"765","DOI":"10.4014\/jmb.2104.04016","article-title":"Bone Homeostasis and Gut Microbial-Dependent Signaling Pathways","volume":"31","author":"Zhong","year":"2021","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"454","DOI":"10.22203\/eCM.v041a29","article-title":"Gut microbial-derived short-chain fatty acids and bone: A potential role in fracture healing","volume":"41","author":"Wallimann","year":"2021","journal-title":"Eur. Cell Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism","volume":"54","author":"Groen","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41575-019-0157-3","article-title":"The role of short-chain fatty acids in microbiota-gut-brain communication","volume":"16","author":"Dalile","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bonr.2018.02.001","article-title":"Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance","volume":"8","author":"Dar","year":"2018","journal-title":"Bone Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108998","DOI":"10.1016\/j.intimp.2022.108998","article-title":"Crosstalk between the gut microbiota and postmenopausal osteoporosis: Mechanisms and applications","volume":"110","author":"Xu","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Liang, X., and Wang, L. (2025). The Mediating Role of Bioactive Molecules in Gut Microbiota-Bone Metabolism Crosstalk. Nutrients, 17.","DOI":"10.3390\/nu17213421"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1172\/JCI128521","article-title":"The gut-bone axis: How bacterial metabolites bridge the distance","volume":"129","author":"Zaiss","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_41","first-page":"16","article-title":"Role of the gut microbiota in the pathogenesis and therapeutic approach to osteoporosis (Review)","volume":"24","author":"Ao","year":"2026","journal-title":"Biomed. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Xue, K., Tao, R., Wu, Q., Zhang, L., Sun, Z., Yu, X., Meng, J., Bao, N., and Zhao, J. (2021). Enteropathogenic Escherichia coli Mediates CoCrMo Particle-Induced Peri-Implant Osteolysis by Increasing Peripheral 5-HT. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.796679"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s40168-017-0271-9","article-title":"Uncovering the trimethylamine-producing bacteria of the human gut microbiota","volume":"5","author":"Rath","year":"2017","journal-title":"Microbiome"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e10452","DOI":"10.1002\/jbm4.10452","article-title":"The gut microbiome is altered in postmenopausal women with osteoporosis and osteopenia","volume":"5","author":"Rettedal","year":"2021","journal-title":"JBMR PLUS"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ying, Z.-H., Mao, C.-L., Xie, W., and Yu, C.-H. (2023). Postbiotics in rheumatoid arthritis: Emerging mechanisms and intervention perspectives. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1290015"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Piccioni, A., Rosa, F., Manca, F., Pignataro, G., Zanza, C., Savioli, G., Covino, M., Ojetti, V., Gasbarrini, A., and Franceschi, F. (2022). Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113323"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Song, M., Zhang, X., Hao, G., Lin, H., and Sun, S. (2023). Clostridium butyricum Can Promote Bone Development by Regulating Lymphocyte Function in Layer Pullets. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021457"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zemanova, N., Omelka, R., Mondockova, V., Kovacova, V., and Martiniakova, M. (2022). Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases. Biology, 11.","DOI":"10.3390\/biology11101402"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yan, Q., Cai, L., and Guo, W. (2022). New advances in improving bone health based on specific gut microbiota. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.821429"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Okoro, P.C., Orwoll, E.S., Huttenhower, C., Morgan, X., Kuntz, T.M., McIver, L.J., Dufour, A.B., Bouxsein, M.L., Langsetmo, L., and Farsijani, S. (2023). A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1237727"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Magne, F., Gotteland, M., Gauthier, L., Zazueta, A., Pesoa, S., Navarrete, P., and Balamurugan, R. (2020). The firmicutes\/bacteroidetes ratio: A relevant marker of gut dysbiosis in obese patients?. Nutrients, 12.","DOI":"10.3390\/nu12051474"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.aninu.2025.05.002","article-title":"Dietary fiber derived short-chain fatty acids as a critical driver of the gut-bone axis in animal bone health: A review","volume":"22","author":"Zulfiqar","year":"2025","journal-title":"Anim. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E344\u201354","DOI":"10.1152\/ajpendo.00366.2021","article-title":"Development of a synbiotic that protects against ovariectomy-induced trabecular bone loss","volume":"322","author":"Lawenius","year":"2022","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/biof.1835","article-title":"Gut microbiome-micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins?","volume":"48","author":"Barone","year":"2022","journal-title":"Biofactors"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Fleet, J.C. (2022). Vitamin D-Mediated Regulation of Intestinal Calcium Absorption. Nutrients, 14.","DOI":"10.3390\/nu14163351"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Bellissimo, M.P., Roberts, J.L., Jones, D.P., Liu, K.H., Taibl, K.R., Uppal, K., Weitzmann, M.N., Pacifici, R., Drissi, H., and Ziegler, T.R. (2020). Metabolomic Associations with Serum Bone Turnover Markers. Nutrients, 12.","DOI":"10.3390\/nu12103161"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00223-024-01329-7","article-title":"Association Between Dietary Tryptophan Intake and Bone Health: A Cross-Sectional Study","volume":"116","author":"Su","year":"2024","journal-title":"Calcif. Tissue Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"707","DOI":"10.20945\/2359-3997000000566","article-title":"Anabolic therapy for osteoporosis: Update on efficacy and safety","volume":"66","author":"Bandeira","year":"2022","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Piazzesi, A., Pane, S., Russo, A., Del Chierico, F., Francalanci, P., Cotugno, N., Rossi, P., Locatelli, F., Palma, P., and Putignani, L. (2023). Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1281440"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/MED.0000000000000863","article-title":"The interaction between gut microbiome and bone health","volume":"31","author":"Inchingolo","year":"2024","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yang, K., Qiu, X., Cao, L., and Qiu, S. (2022). The role of melatonin in the development of postmenopausal osteoporosis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.975181"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1007\/s11914-023-00824-4","article-title":"Inflammatory processes affecting bone health and repair","volume":"21","author":"Torres","year":"2023","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10856-015-5538-8","article-title":"Effect of silver nanoparticle geometry on methicillin susceptible and resistant Staphylococcus aureus, and osteoblast viability","volume":"26","author":"Actis","year":"2015","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1177\/0260106019866963","article-title":"Design and baseline characteristics of the Biomarkers Of Risk In Colorectal Cancer (BORICC) Follow-Up study: A 12+ years follow-up","volume":"25","author":"Malcomson","year":"2019","journal-title":"Nutr. Health"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1042\/CS20171107","article-title":"Altered microbiome in chronic kidney disease: Systemic effects of gut-derived uremic toxins","volume":"132","author":"Lau","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.4049\/jimmunol.1302286","article-title":"Probiotic Lactobacillus rhamnosus inhibits the formation of neutrophil extracellular traps","volume":"192","author":"Vong","year":"2014","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bungau, S.G., Behl, T., Singh, A., Sehgal, A., Singh, S., Chigurupati, S., Vijayabalan, S., Das, S., and Palanimuthu, V.R. (2021). Targeting probiotics in rheumatoid arthritis. Nutrients, 13.","DOI":"10.3390\/nu13103376"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Harahap, I.A., and Suliburska, J. (2021). Probiotics and isoflavones as a promising therapeutic for calcium status and bone health: A narrative review. Foods, 10.","DOI":"10.3390\/foods10112685"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Chen, Y., Wang, X., Zhang, C., Liu, Z., Li, C., and Ren, Z. (2022). Gut microbiota and bone diseases: A growing partnership. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.877776"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Siddiqui, R., Makhlouf, Z., Alharbi, A.M., Alfahemi, H., and Khan, N.A. (2022). The gut microbiome and female health. Biology, 11.","DOI":"10.3390\/biology11111683"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1007\/s00198-022-06557-x","article-title":"The potential mechanism of the microbiota-gut-bone axis in osteoporosis: A review","volume":"33","author":"He","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/jbmr.4194","article-title":"Effects of High-Dose Vitamin D Supplementation on Bone Fragility","volume":"36","author":"Sugiyama","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e13475","DOI":"10.1016\/j.heliyon.2023.e13475","article-title":"Probiotics and metabolites regulate the oral and gut microbiome composition as host modulation agents in periodontitis: A narrative review","volume":"9","author":"Deandra","year":"2023","journal-title":"Heliyon"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s00223-022-00975-z","article-title":"Lactobacillus rhamnosus GG Promotes Intestinal Vitamin D Absorption by Upregulating Vitamin D Transporters in Senile Osteoporosis","volume":"111","author":"Cheng","year":"2022","journal-title":"Calcif. Tissue Int."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/17461391.2021.1921853","article-title":"More than a gut feeling: What is the role of the gastrointestinal tract in female athlete health?","volume":"22","author":"Pugh","year":"2022","journal-title":"Eur. J. Sport Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1007\/s11427-021-2103-5","article-title":"Interactions between central nervous system and peripheral metabolic organs","volume":"65","author":"Zeng","year":"2022","journal-title":"Sci. China Life Sci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ibrahim, I., Syamala, S., Ayariga, J.A., Xu, J., Robertson, B.K., Meenakshisundaram, S., and Ajayi, O.S. (2022). Modulatory Effect of Gut Microbiota on the Gut-Brain, Gut-Bone Axes, and the Impact of Cannabinoids. Metabolites, 12.","DOI":"10.20944\/preprints202210.0465.v1"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2459\/JCM.0000000000000900","article-title":"Microbiome and hypertension: Where are we now?","volume":"21","author":"Vallianou","year":"2020","journal-title":"J. Cardiovasc. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1161\/CIRCRESAHA.116.307709","article-title":"Brain-Gut-Bone Marrow Axis: Implications for Hypertension and Related Therapeutics","volume":"118","author":"Santisteban","year":"2016","journal-title":"Circ. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41421-025-00853-6","article-title":"Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases","volume":"12","author":"Zhu","year":"2026","journal-title":"Cell Discov."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"9048","DOI":"10.3168\/jds.2025-26730","article-title":"Butyrate-producing Lactococcus lactis-fermented goat cheese enhances bone health and reduces osteoporotic bone loss","volume":"108","author":"Liu","year":"2025","journal-title":"J. Dairy Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1292\/jvms.13-0229","article-title":"Role of collagen and inorganic components in electrical polarizability of bone","volume":"76","author":"Hiratai","year":"2014","journal-title":"J. Vet. Med. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e70281","DOI":"10.1002\/mco2.70281","article-title":"Extracellular matrix signaling cues: Biological functions, diseases, and therapeutic targets","volume":"6","author":"Zhao","year":"2025","journal-title":"MedComm"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ke, K., Arra, M., and Abu-Amer, Y. (2019). Mechanisms Underlying Bone Loss Associated with Gut Inflammation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246323"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1038\/s41418-019-0312-y","article-title":"Gut microbiota-stimulated cathepsin K secretion mediates TLR4-dependent M2 macrophage polarization and promotes tumor metastasis in colorectal cancer","volume":"26","author":"Li","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.3390\/jcm8101753","article-title":"Oral-Gut Microbiota and Arthritis: Is There an Evidence-Based Axis?","volume":"8","author":"Lorenzo","year":"2019","journal-title":"J. Clin. Med."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Forte, Y.S., Renovato-Martins, M., and Barja-Fidalgo, C. (2023). Cellular and molecular mechanisms associating obesity to bone loss. Cells, 12.","DOI":"10.3390\/cells12040521"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Williams, K.L., Enslow, R., Suresh, S., Beaton, C., Hodge, M., and Brooks, A.E. (2023). Using the microbiome as a regenerative medicine strategy for autoimmune diseases. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061582"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Schiellerup, S.P., Skov-Jeppesen, K., Windel\u00f8v, J.A., Svane, M.S., Holst, J.J., Hartmann, B., and Rosenkilde, M.M. (2019). Gut hormones and their effect on bone metabolism. potential drug therapies in future osteoporosis treatment. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00075"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Kwon, Y., Park, C., Lee, J., Park, D.H., Jeong, S., Yun, C.-H., Park, O.-J., and Han, S.H. (2021). Regulation of Bone Cell Differentiation and Activation by Microbe-Associated Molecular Patterns. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115805"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.dsx.2020.09.026","article-title":"Pathophysiological mechanisms underlying MAFLD","volume":"14","author":"Kuchay","year":"2020","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Wang, Y., Ze, X., Rui, B., Li, X., Zeng, N., Yuan, J., Li, W., Yan, J., and Li, M. (2021). Studies and application of sialylated milk components on regulating neonatal gut microbiota and health. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.766606"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/6\/909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T04:30:17Z","timestamp":1780115417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/6\/909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":93,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["life16060909"],"URL":"https:\/\/doi.org\/10.3390\/life16060909","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}