Kaiser Jamil¹*, Sufiya Kouser^1,2, Kareem Unnisa^1,2, Syeda Madiha Fatima^1,2, Sheefa Ulain^1,2, Naseerah Maryam², Mohd Abdul Aziz Shahid² and Shivakumar Yerra³

¹Genetics Department, Bhagwan Mahavir Medical Research Centre, TS, India
²Shahdan Women’s College of Pharmacy, Hyderabad, TS, India
³Head of Cardiology Department, Mahavir Hospital and Research Centre, TS, India

*Corresponding Author: Kaiser Jamil, Genetics Department, Bhagwan Mahavir Medical Research Centre, TS, India.

Received: January 02, 2026; Published: March 20, 2026

The gut microbiota plays a pivotal role in maintaining bone homeostasis through nutrient absorption, immune modulation, endocrine regulation and microbial metabolite production. Dysbiosis, a disruption of this ecosystem, is increasingly recognised as a key contributor to osteoporosis, a metabolic disorder defined by low bone mineral density (BMD) and micro-architectural deterioration. Recent insights into the gut–bone axis reveal that microbial metabolites such as short-chain fatty acids (SCFAs), immune regulators like IL-17 and TNF-α, and intestinal barrier integrity profoundly influence bone remodelling. This review explores the mechanisms linking gut dysbiosis to osteoporosis, examines preclinical and clinical evidence supporting this interaction, and discusses microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and postbiotics. Emerging multi-omics and AI-driven approaches further support the translational potential of personalised, microbiome-informed osteoporosis care. Understanding and modulating the osteomicrobiome may open new avenues for prevention and precision treatment of osteoporosis.

Keywords: Osteomicrobiome; Osteoporosis; Gut–Bone Axis; Dysbiosis; Short-Chain Fatty Acids; Probiotics; Bone Metabolism

References

1. Kanis John A., et al. “European guidance for the diagnosis and management of osteoporosis in postmenopausal women”. Osteoporosis International1 (2019): 3-44.
2. Compston Juliet E., et al. “Osteoporosis”. The Lancet10169 (2019): 364-376.
3. Xu Xiaomin., et al. “The gut microbiota and bone health: Linking microbial composition to osteoporosis. Nature Reviews Endocrinology5 (2021): 295-310.
4. Panach Lidia and Rosell-Valle Carolina. “Molecular pathology, diagnostics, and therapeutics of osteoporosis”. International Journal of Molecular Sciences19 (2023): 14583.
5. Weaver Connie M and Martin Brandi R. “Gut microbiome’s influence on bone metabolism and health. Current Osteoporosis Reports 18.3 (2020): 134-142.
6. com. (n.d.). Healthy microbiome vs. dysbiosis Infographic (2025).
7. Tang H., et al. “Escherichia coli lipopolysaccharides inhibit osteoblast differentiation and promote osteoclastogenesis through NF κB signaling”. Journal of Translational Medicine 19 (2021): 386.
8. Chen X., et al. “Exploring the role of intestinal pathogenic bacteria in metronidazole-induced bone loss: Focus onKlebsiella variicola”. Gut Pathogens 17 (2025): Article 42.
9. Jha SS., et al. “Gut microbiome and orthopaedic health: Mechanism of dysbiosis-induced bone loss”. World Journal of Orthopedics12 (2024): 102274.
10. Sjögren K., et al. “Gut microbiota regulate bone mass in mice: The gut-bone axis”. Proceedings of the National Academy of Sciences (PNAS)39 (2012): 15422-15427.
11. Xu J and Zhang Y. “The gut microbiota in osteoporosis: dual roles and therapeutic prospects”. Cell Proliferation (2025).
12. Wu W., et al. “Gut microbiota modulates osteoclast glutathione synthesis and mitochondrial biogenesis in mice subjected to ovariectomy”. Cell Proliferation1 (2021): e12804.
13. Gong Y., et al. “Akkermansia muciniphila and osteoporosis: emerging role of gut microbiota in skeletal homeostasis”. Frontiers in Microbiology 16 (2025): 1665101.
14. Jeyaraman N., et al. “Gut microbiome and orthopaedic health: Mechanisms linking dysbiosis to bone loss and fracture risk”. World Journal of Orthopedics12 (2024): 1135-1149.
15. Animal Diseases Consortium. “Gut microbiota as a target in the bone health of livestock and poultry: roles of short chain fatty acids”. Animal Diseases (2023).
16. Cross talks between osteoporosis and gut microbiome. “Review article. Summarizes gut bone axis mechanisms, including LPS and dysbiosis-related inflammation as contributors to bone loss” (2025).
17. Gu Chunli., et al. “The gut-bone axis in osteoporosis: A multifaceted interaction with implications for bone health”. Frontiers in Endocrinology 16 (2025): Article 1569152.
18. Picca Antonio and Marzetti Ettore. “Gut microbiota dysbiosis and its relation to osteoporosis and sarcopenia in older people”. Aging Clinical and Experimental Research (2024).
19. Hwang Jin Su., et al. “Microbiome metabolic products as regulators of bone metabolism: Diet, supplementation, and engineered microbes for skeletal health”. Frontiers in Endocrinology 16 (2025).
20. Hernandez C., et al. “Therapeutic strategies targeting the gut-bone axis in osteoporosis”. Journal of Bone and Mineral Research9 (2022): 1723-1737.
21. Jiao Y., et al. “Probiotics and bone health: Mechanistic insights and clinical evidence”. Nutrients12 (2021): 4275.
22. Nilsson A., et al. “Lactobacillus reuteri supplementation improves bone density in postmenopausal women: A randomized clinical trial”. Journal of Clinical Endocrinology and Metabolism10 (2020): e3672-e3682.
23. Rizzoli R., et al. “Prebiotics and synbiotics for bone health: Current evidence and future perspectives”. Osteoporosis International10 (2021): 1963-1977.
24. Lucas S., et al. “Microbiota-derived metabolites in bone metabolism: Focus on SCFAs and postbiotics”. Cell Metabolism7 (2021): 1334-1350.
25. Zhou X., et al. “Fecal microbiota transplantation as a potential therapy for osteoporosis: Evidence from preclinical studies”. Frontiers in Endocrinology 13 (2022): 884123.
26. García-Larsen V and Ash S. “Polyphenols and bone health: Modulation of gut microbiota and clinical implications”. Nutrients7 (2022): 1425.
27. Li Z., et al. “Pharmacobiotics in osteoporosis: Combining probiotics with conventional therapies”. Frontiers in Endocrinology 13 (2022): 902345.
28. Shen L and Zhang D. “Lifestyle interventions for osteoporosis prevention: Diet, exercise, and gut microbiome modulation”. Journal of Bone and Mineral Metabolism6 (2021): 1015-1032.
29. Wang Y., et al. “Gut microbiome and skeletal health: Advances in multi-omics research”. Nature Reviews Endocrinology5 (2029): 287-302.
30. Kim S., et al. “Integrative metagenomics and metabolomics reveal gut-bone interactions in osteoporosis”. Gut Microbes 1 (2024): 2160456.
31. Singh P., et al. “Medication-induced microbiome disruption and bone health: Emerging evidence”. Osteoporosis International6 (2023): 1201-1216.
32. Zhao X., et al. “Next-generation probiotics in bone metabolism: Akkermansia muciniphila and beyond”. Frontiers in Cellular and Infection Microbiology 13 (2023): 1189347.
33. Liu Y., et al. “Machine learning for microbiome-based prediction of osteoporosis and fracture risk”. Computational Biology and Medicine 162 (2024): 106985.
34. Patel N., et al. “Precision medicine in osteoporosis: The role of gut-microbiome signatures”. Journal of Translational Medicine1 (2023): 392.
35. Xu H., et al. “Clinical translation of the gut-bone axis: Implications for osteoporosis management”. Journal of Translational Medicine1 (2023): 412.
36. Fernández-Ruiz V and García-Sanz M. “Microbiome-based biomarkers for early detection of bone loss”. Bone Reports 19 (2023): 101365.
37. Huang Y., et al. “Gut-directed therapies in high-risk osteoporosis populations: Current evidence and future directions”. Frontiers in Endocrinology 13 (2022): 945672.
38. Khan R., et al. “Male osteoporosis: Gut microbiome contributions and therapeutic perspectives”. Osteoporosis International12 (2021): 2415-2429.
39. González A., et al. “Childhood antibiotic exposure, gut microbiota, and long-term bone health”. Nutrients 4 (2023): 889.
40. Martin A and Brown K. “Limitations and challenges in translating gut microbiome research to clinical practice in osteoporosis”. Current Osteoporosis Reports 3 (2022): 135-149.
41. Singh R and Kumar P. “Methodological heterogeneity in osteomicrobiome studies: Implications for reproducibility”. Gut Microbes 1 (2023): 2180904.
42. O’Connor L and Zhao H. “Safety and regulatory considerations for microbiome-based interventions in bone diseases”. Frontiers in Pharmacology 12 (2021): 709872.

Citation

Citation: Kaiser Jamil., et al. “Unravelling the Osteo-microbiome: Gut-Bone Axis in Osteoporosis Pathogenesis and Therapeutic Options". Acta Scientific Medical Sciences 10.4 (2026): 03-15.

Copyright

Copyright: © 2026 Kaiser Jamil., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.