Gut microbiota-immune-bone axis in osteoporosis: mechanisms and intervention strategies
- 1Department of Pharmacy, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital, Guangzhou Medical University
- 2Department of Pharmacy, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People’s Hospital)
- 3Department of Pharmacy, Central Hospital of Guangdong Prison
Abstract
Osteoporosis (OP) remains a major global health burden, yet current pharmacological interventions are constrained by adverse effects, limited efficacy, and a bone-centric therapeutic paradigm that overlooks upstream pathogenic drivers. Emerging evidence positions the gut microbiota (GM) as a critical rheostat of bone homeostasis, operating through a gut–immune–bone axis that integrates microbial metabolism, intestinal barrier integrity, and systemic immune regulation. This review systematically examines the immunopathological mechanisms of OP, with particular emphasis on the GM-derived metabolites—short-chain fatty acids, secondary bile acids, tryptophan derivatives, lipopolysaccharide, and trimethylamine N-oxide—that orchestrate osteoclastogenic versus osteoprotective outcomes via key immune checkpoints including the Th17/Treg, macrophage phenotypic polarization, and regulatory B cell axes. We further delineate the subtype-specific heterogeneity of this axis across postmenopausal, senile, glucocorticoid-induced, and diabetic osteoporosis, highlighting distinct microbial and immune signatures that mandate stratified therapeutic approaches. Importantly, we evaluate the translational potential of GM-targeted interventions—probiotics, prebiotics, fecal microbiota transplantation, and dietary modulation—as adjunctive or standalone strategies, and discuss their synergistic interplay with conventional anti-osteoporotic agents. By reframing OP as a systems-level disorder of the gut–immune–bone circuitry, this review establishes a mechanistic groundwork for precision medicine, identifies novel druggable targets, and charts a course toward safer, more durable, and disease-modifying anti-osteoporotic therapies.
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BibTeX
@article{huang2026microbiotaimmunebone,
title = {{Gut microbiota-immune-bone axis in osteoporosis: mechanisms and intervention strategies}},
author = {Minying Huang and Baocheng Xie and Hongyu Liu},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1879472},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1879472/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gut microbiota-immune-bone axis in osteoporosis: mechanisms and intervention strategies
AU - Minying Huang
AU - Baocheng Xie
AU - Hongyu Liu
PY - 2026
DA - 2026/10/09
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1879472
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1879472/full
AB - Osteoporosis (OP) remains a major global health burden, yet current pharmacological interventions are constrained by adverse effects, limited efficacy, and a bone-centric therapeutic paradigm that overlooks upstream pathogenic drivers. Emerging evidence positions the gut microbiota (GM) as a critical rheostat of bone homeostasis, operating through a gut–immune–bone axis that integrates microbial metabolism, intestinal barrier integrity, and systemic immune regulation. This review systematically examines the immunopathological mechanisms of OP, with particular emphasis on the GM-derived metabolites—short-chain fatty acids, secondary bile acids, tryptophan derivatives, lipopolysaccharide, and trimethylamine N-oxide—that orchestrate osteoclastogenic versus osteoprotective outcomes via key immune checkpoints including the Th17/Treg, macrophage phenotypic polarization, and regulatory B cell axes. We further delineate the subtype-specific heterogeneity of this axis across postmenopausal, senile, glucocorticoid-induced, and diabetic osteoporosis, highlighting distinct microbial and immune signatures that mandate stratified therapeutic approaches. Importantly, we evaluate the translational potential of GM-targeted interventions—probiotics, prebiotics, fecal microbiota transplantation, and dietary modulation—as adjunctive or standalone strategies, and discuss their synergistic interplay with conventional anti-osteoporotic agents. By reframing OP as a systems-level disorder of the gut–immune–bone circuitry, this review establishes a mechanistic groundwork for precision medicine, identifies novel druggable targets, and charts a course toward safer, more durable, and disease-modifying anti-osteoporotic therapies.
SN - 1663-9812
ER -