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.
摘要：
最近，人们对肠道微生物组在调节脊椎动物代谢中的作用表示赞赏。然而,肠道菌群对骨骼生长和体内平衡的影响最近才开始被研究。这里,我们报告说，定植性成熟的无菌（GF）小鼠与常规的特定无病原体（SPF）肠道微生物群增加骨形成和再吸收，定殖的净效应随定殖的持续时间而变化。尽管成年小鼠的定植会急剧减少骨量，在长期定植的小鼠中，骨形成和生长板活动的增加占主导地位，导致骨量均衡，纵向和桡骨生长增加。血清胰岛素样生长因子1(IGF-1)水平,一种对骨骼生长有已知作用的激素，对微生物定植的反应大大增加，肝脏和脂肪组织IGF-1产量显著增加。常规小鼠的抗生素治疗，相比之下,降低血清IGF-1并抑制骨形成。用短链脂肪酸（SCFA）补充抗生素治疗的小鼠，微生物代谢产物，将IGF-1和骨量恢复到非抗生素治疗小鼠的水平。因此，SCFA的产生可能是微生物群增加血清IGF-1的一种机制。我们的研究表明，肠道微生物群为骨骼提供了净合成代谢刺激，这可能是由IGF-1介导的。微生物组或其代谢物的操纵可以提供优化骨骼健康和生长的机会。
