Gut Microbiota-Bone Axis.

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Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field of such great interest. Recent studies have reported that communities of microorganisms inhabiting the gut influence the immune system through cellular responses and shape many physiological and pathophysiological aspects of the body, including muscle and bone metabolism (formation and resorption). Specifically, the gut microbiota affects skeletal homeostasis through changes in host metabolism, the immune system, hormone secretion, and the gut-brain axis. The major role on gut-bone axis is due to short-chain fatty acids (SCFAs). They have the ability to influence regulatory T-cell (Tregs) development and activate bone metabolism through the action of Wnt10. SCFA production may be a mechanism by which the microbial community, by increasing the serum level of insulin-like growth factor 1 (IGF-1), leads to the growth and regulation of bone homeostasis. A specific SCFA, butyrate, diffuses into the bone marrow where it expands Tregs. The Tregs induce production of the Wnt ligand Wnt10b by CD8+ T cells, leading to activation of Wnt signaling and stimulation of bone formation. At the hormonal level, the effect of the gut microbiota on bone homeostasis is expressed through the biphasic action of serotonin. Some microbiota, such as spore-forming microbes, regulate the level of serotonin in the gut, serum, and feces. Another group of bacterial species (Lactococcus, Mucispirillum, Lactobacillus, and Bifidobacterium) can increase the level of peripheral/vascular leptin, which in turn manages bone homeostasis through the action of brain serotonin.