Gut microbiota induce IGF-1 and promote bone formation and growth

Yan, Jing; Herzog, Jeremy W.; Tsang, Kelly; Brennan, Caitlin A.; Bower, Maureen A.; Garrett, Wendy S.; Sartor, Balfour R.; Aliprantis, Antonios O.; Charles, Julia F.

doi:10.1073/pnas.1607235113

Cited by 755Gut microbiota and healthBone Metabolism and DiseasesGrowth Hormone and Insulin-like Growth Factors

Gut microbiota induce IGF-1 and promote bone formation and growth

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Yan, Jing, Herzog, Jeremy W., Tsang, Kelly, Brennan, Caitlin A., Bower, Maureen A., Garrett, Wendy S., Sartor, Balfour R., Aliprantis, Antonios O. +1 more·2016·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1607235113PMC PMC5127374

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Abstract

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, which may contribute to age-associated pathologies and negatively affect host health.
“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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Diets intervene osteoporosis via gut-bone axis
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RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis
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Coix seed polysaccharides alleviate type 2 diabetes mellitus via gut microbiota-derived short-chain fatty acids activation of IGF1/PI3K/AKT signaling
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Secretome of Intestinal Bacilli: A Natural Guard against Pathologies
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STING suppresses bone cancer pain via immune and neuronal modulation
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The Association of Gut Microbiota With Osteoporosis Is Mediated by Amino Acid Metabolism: Multiomics in a Large Cohort
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Captivity and Animal Microbiomes: Potential Roles of Microbiota for Influencing Animal Conservation
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Gut Microbiome and Osteoporosis
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Berberine Ameliorates Periodontal Bone Loss by Regulating Gut Microbiota
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Gut Microbiota and IGF-1
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Commensal gut microbiota immunomodulatory actions in bone marrow and liver have catabolic effects on skeletal homeostasis in health
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Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice
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Gut microbiota and bone metabolism
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A Review of Chondroitin Sulfate’s Preparation, Properties, Functions, and Applications
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Therapeutic potentials and modulatory mechanisms of fatty acids in bone
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The Interplay between Immune System and Microbiota in Osteoporosis
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Bone diseases in patients with chronic liver disease
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Comparison of different modes of antibiotic delivery on gut microbiota depletion efficiency and body composition in mouse
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Gut microbial-derived short-chain fatty acids and bone: a potential role in fracture healing
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Microbial osteoporosis: The interplay between the gut microbiota and bones via host metabolism and immunity
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“However, 8 months after colonization, the effect on bone formation was dominant, leading to increased bone mineral density of longitudinal and ra‐ dial bones (Yan et al., 2016).”
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Gut microbiome and bone: To build, destroy, or both?
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Osteoarthritis induced by destabilization of the medial meniscus is reduced in germ-free mice
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Pueraria lobata-derived exosome-like nanovesicles alleviate osteoporosis by enhacning autophagy
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From osteoimmunology to osteomicrobiology: How the microbiota and the immune system regulate bone
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Are Probiotics the New Calcium and Vitamin D for Bone Health?
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Gut microbiota modulates osteoclast glutathione synthesis and mitochondrial biogenesis in mice subjected to ovariectomy
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Gut microbiome and bone
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The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases
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Organ-organ communication: The liver's perspective
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Bone Remodeling and the Microbiome
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Tetracyclines and bone: Unclear actions with potentially lasting effects
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Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome
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Fecal dysbiosis in infants with cystic fibrosis is associated with early linear growth failure
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Gut microbiota develop towards an adult profile in a sex-specific manner during puberty
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Crosstalk between the gut microbiota and postmenopausal osteoporosis: Mechanisms and applications
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Metabolic Cooperation among Commensal Bacteria Supports Drosophila Juvenile Growth under Nutritional Stress
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Gut microbiota alterations and dietary modulation in childhood malnutrition – The role of short chain fatty acids
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Supportive Role of Probiotic Strains in Protecting Rats from Ovariectomy-Induced Cortical Bone Loss
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High animal protein diet and gut microbiota in human health
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Regulation of bone mass by the gut microbiota is dependent on NOD1 and NOD2 signaling.
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Ferrosenescence: The iron age of neurodegeneration?
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Road MAPs to engineer host microbiomes
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The Gut Microbiota Affects Host Pathophysiology as an Endocrine Organ: A Focus on Cardiovascular Disease
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Short-chain fatty acids and FFAR2 as suppressors of bone resorption
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Synergistic effects of fermented soybean meal and mannan-oligosaccharide on growth performance, digestive functions, and hepatic gene expression in broiler chickens
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Gut microbiota promote bone growth via IGF1
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40 YEARS OF IGF1: The emerging connections between IGF1, the intestinal microbiome, Lactobacillus strains and bone growth
Poinsot, P., Schwarzer, M., Peretti, N., & Leulier, F. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0292 · Cited by 29 · see citing works
Reconstitution of the host holobiont in germ-free rats acutely increases bone growth and affects marrow cellular contentPreprint
Czernik, P., Golonka, R., Chakraborty, S., Yeoh, B., Abokor, A., Saha, P., Yeo, J., Mell, B., Cheng, X., Baroi, S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.15.201657 · Cited by 1 · see citing works
Reconstitution of the host holobiont in germ-free born male rats acutely increases bone growth and affects marrow cellular content
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Gut Microbiota-Bone Axis
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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: Yan, Jing
Herzog, Jeremy W.
Brennan, Caitlin A.
Garrett, Wendy S.
Aliprantis, Antonios O.
Charles, Julia F.
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
DOI: 10.1073/pnas.1607235113
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 · 2015: 1 · 2013: 1
FWCI: 22.36
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.pnas.org/site/misc/userlicense.xhtml (vor, 181 d)
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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Gut microbiota induce IGF-1 and promote bone formation and growth

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