5bd97c2c56daeca9b3417e0b7e282f51 life-16-00909.pdf 2e6c196d17b120cf1fb9e0fc0ab929668622b839 life-16-00909.pdf 32cf872d6ba0d3050f200b8bea9c009f3dc9a3105658677231dab25b25134e64 life-16-00909.pdf Title: The Gut–Bone Axis: A Systematic Review on the Potential Intervention Pathways for Bone Health Subject: 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–brain–bone 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 -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. Keywords: gut–bone axis; gut–brain–bone axis; bone health; osteoporosis; probiotics; gut microbiota; extracellular matrix; metabolites Author: Tomás Cantón-Cordeiro, Saeka Shimochi, Miho Nakamura and Pere Puigbò Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Thu May 28 13:08:29 2026 CEST ModDate: Thu May 28 13:12:29 2026 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1242324 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLFTRW+VnURWPalladioL-Bold Type 1 Custom yes yes yes 164 0 YERPJW+URWPalladioL-Ital Type 1 Custom yes yes yes 165 0 QDULQU+EURM10 Type 1 Builtin yes yes yes 166 0 CNAXAH+URWPalladioL-Bold Type 1 Custom yes yes yes 167 0 CSMNZN+URWPalladioL-Roma Type 1 Custom yes yes yes 168 0 AHELBE+PalatinoLinotype TrueType WinAnsi yes yes no 252 0 AHELBC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 253 0 AHELBE+PalatinoLinotype TrueType WinAnsi yes yes no 282 0 VBUSXR+PazoMath-Italic Type 1 Builtin yes yes yes 371 0 MIKRSI+VnURWPalladioL Type 1 Custom yes yes yes 615 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-06-17 03:57:32 CEST RepresentationInformation: life-16-00909.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-06-16 14:46:48 CEST Size: 1242324 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 781 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Children: Item: Title: Background Item: Title: Osteoporosis Disease Item: Title: The Gut–Bone and Gut–Brain–Bone Axes Item: Title: Scope and Search Strategies in the Semi-Automated Systematic Review Children: Item: Title: Automating a Systematic Review Item: Title: Databases and Search Strategies Item: Title: Generation of Keywords Item: Title: Specific Criteria Item: Title: Iterative Filtering for Classification Item: Title: Data Extraction Item: Title: Quality Control Item: Title: Results and Discussion Children: Item: Title: Potential Targets Within the Gut–Bone Axis Children: Item: Title: Native Bacteria Supporting Bone Formation Item: Title: Native Bacteria Promoting Bone Resorption Item: Title: Metabolites Involved in Bone Health Item: Title: Probiotics as Potential Intervention Treatment for Osteoporosis and Bone Related Diseases Item: Title: Case of Study: Lactobacillus rhamnosus GG (LGG) Item: Title: Potential Targets Within the Gut–Brain–Bone Axis Item: Title: Bone ECM Proteins as Mediators of the Gut–(Brain)–Bone Axes Children: Item: Title: Osteopontin Item: Title: Cathepsin K Item: Title: Limitations Item: Title: Conclusions Item: Title: References Info: Title: The Gut–Bone Axis: A Systematic Review on the Potential Intervention Pathways for Bone Health Author: Tomás Cantón-Cordeiro, Saeka Shimochi, Miho Nakamura and Pere Puigbò Subject: 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–brain–bone 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 -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. 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