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Gut microbiota induce IGF-1 and promote bone formation and growth
Open accessAbstract
Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.
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“Unhealthy perturbations in gut microbiota are related to disrupted host nutrient signaling pathways and metabolism (45), which may contribute to age-associated pathologies, thereby negatively affecting host health (46).”
From Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice (2021) · cites this paper as [45]
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Metadata
- Authors
- Yan, J., Herzog, J. W., Tsang, K., Brennan, C. A., Bower, M. A., Garrett, W. S., Sartor, B. R., Aliprantis, A. O., & Charles, J. F.
- Affiliations
- Brigham and Women's Hospital (US)
- University of North Carolina at Chapel Hill (US)
- Harvard University (US)
- Broad Institute (US)
- National Gnotobiotic Rodent Resource Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
- Corresponding author
- Charles, Julia F.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-11-07
- Volume
- 113
- Issue
- 47
- Pages
- E7554-E7563
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5127374
- OpenAlex
- W2556090133
- Cited by
- 750
- References
- 65
- Citations by year
- 2026: 83 · 2025: 94 · 2024: 110 · 2023: 94 · 2022: 76 · 2021: 93 · 2020: 67 · 2019: 52 · 2018: 46 · 2017: 29 · 2016: 2
- FWCI
- 22.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute on Aging (AG046257)
- HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR062590)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK034987)
- HHS | NIH | NIH Office of the Director (5-P40-OD010995)
- HHS | NIH | National Cancer Institute (CA154426)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- gut microbiota, insulin-like growth factor I, bone formation, bone growth, bone mass, germ-free mice, microbial colonization, bone resorption, growth plate, short-chain fatty acids, antibiotic therapy, bone health, skeletal development
- MeSH terms
- Gastrointestinal Microbiome, Adipose Tissue, Animals, Bone and Bones, Bone Development, Fatty Acids, Volatile, Female, Insulin-Like Growth Factor I, Liver, Male, Osteogenesis, Specific Pathogen-Free Organisms, Mice
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