Gut Microbiome and Bone: to Build, Destroy, or Both?
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Purpose of Review
The gut microbiota can be considered a hidden organ that plays essential roles in host homeostasis. Exploration of the effects of microbiota on bone has just begun. Complimentary studies using germ-free mice, antibiotic, and probiotic treatments reveal a complicated relationship between microbiota and bone. Here, we review recent reports addressing the effect of gut microbiota on bone health, discuss potential reasons for discrepant findings, and explore potential mechanisms for these effects.
Manipulation of microbiota by colonization of germ-free mice, antibiotics, or probiotic supplementation significantly alters bone remodeling, bone development and growth, as well as bone mechanical strength. Different experimental models reveal context-dependent effects of gut microbiota on bone.
By examining phenotypic effects, experimental context, and proposed mechanisms, revealed by recent reports, we hope to provide comprehensive and fresh insights into the many facets of microbiota and bone interactions.
KeywordsMicrobiome Bone Germ-free Antibiotics Probiotics IGF-1 SCFA
This work was supported by NIH grants AG046257 from the NIA, AR062590 from the NIAMS, a Faculty Career Development Award from the Brigham and Women’s Hospital, and the Bettina Looram Fund.
Compliance with Ethical Standards
Conflict of Interest
Julia Charles and Jing Yan declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 7.•• Sjogren K, et al. The gut microbiota regulates bone mass in mice. J Bone Miner res. 2012;27:1357–67. doi: 10.1002/jbmr.1588. This is the first study using germ-free mice to investigate the effect of microbiota on bone remodeling and to suggest a link between microbiota-mediated effects on the immune system and a pro-osteoclastogenic bone marrow microenvironment. CrossRefPubMedPubMedCentralGoogle Scholar
- 8.•• Yan J, et al. Gut microbiota induce IGF-1 and promote bone formation and growth. Proc Natl Acad Sci U S a. 2016;113:E7554–63. doi: 10.1073/pnas.1607235113. This study comprehensively evaluates the bone phenotype of both germ-free mice colonized with conventional microbiota and SPF mice treated with antibiotics and demonstrates that microbiota promote both bone formation and resorption with the net effect on bone depending on duration of colonization. These studies further suggest that the effects of microbiota on bone are mediated by induction of systemic IGF-1, possibly by SCFA.
- 9.•• Li JY, et al. Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics. J Clin Invest. 2016;126:2049–63. doi: 10.1172/JCI86062. This study demonstrates links between sex hormone deficiency, decreased gut permeability, and pro-osteoclastogenic cytokine production. It also provides data suggesting beneficial effects of probiotics on bone loss caused by sex steroid deprivation.
- 10.•• Schwarzer M, et al. Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science. 2016;351:854–7. doi: 10.1126/science.aad8588. This study demonstrated that neonatal growth and systemic IGF-1 are greater in SPF mice compared to germ-free mice. Further, they identified that monocolonization with a specific bacterial strain is sufficient to alter the growth hormone-IGF-1 axis and positively impact bone growth in mice under conditions of undernutrition. CrossRefPubMedGoogle Scholar
- 23.Guss JD, et al. Alterations to the gut microbiome impair bone strength and tissue material properties. J Bone Miner res. 2017; doi: 10.1002/jbmr.3114.
- 33.Blanton, L. V. et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016; 351: doi: 10.1126/science.aad3311.
- 50.Clements, S. J. & Carding, S. R. Diet, the intestinal microbiota and immune health in ageing. Crit Rev Food Sci Nutr. 2016; 0: doi: 10.1080/10408398.2016.1211086.