Background/Purpose: 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 been explored.

Methods: To understand the effects of short-term and long-term colonization of microbiota on bone, we colonized sexually mature germ-free (GF) mice with gut microbiota from SPF mice. In complementary experiments, SPF mice were treated with antibiotics to deplete microbiota. Bone parameters were examined by micro-computed tomography (micro-CT) and histomorphometry 1 month after colonization. Micro-CT analysis was also performed 8 months after colonization. Serum C-terminal telopeptide (CTX), amino-terminal propeptide (P1NP) and insulin like growth factor 1 (IGF-1) were measured by ELISA.

Results: Reduced bone mass was observed one month after colonization, reflecting increases in bone resorption as measured by CTX. However, bone formation was significantly increased. Increased bone formation was demonstrated by both elevated bone formation rate measured by dynamic histomorphometry and increases in serum P1NP, a marker of bone formation. In addition, short-term colonized mice displayed a widen growth plate, suggesting that microbiota promotes longitudinal bone growth. In mice colonized for 8 months, increased bone formation and growth plate activity predominate, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of IGF-1, a hormone with known actions on skeletal growth, were substantially increased in response to colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreased serum IGF-1 and inhibited bone formation, suggesting that skeletal effects of microbiota are mediated by IGF-1. Treatment with vancomycin, a non-absorbable antibiotic that only targets gram positive bacteria, was sufficient to decrease serum IGF-1 and inhibit bone formation, indicating that gram positive commensals are sufficient for the regulation of bone formation by microbiota.

Conclusion: Colonization increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Long-term colonization with microbiota provides a net anabolic stimulus to the skeleton, which is likely regulated by IGF-1. Manipulation of the microbiome may afford opportunities to optimize bone health and growth.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gut-microbiota-induce-igf-1-and-promote-bone-formation-and-growth/