Figure 2. Effect of gut microbiota on bone homeostasis via biphasic action of serotonin.
(A) Certain microbiota such as spore-forming microbes regulates the level of serotonin in gut, serum and fecal matters. This released serotonin binds to the htr1b receptor of osteoblasts membrane and regulates its proliferation via Htr1b/PKA/CREB/cyclins signaling. (B) Another group of bacterial species (Lactococcus, Mucispirillum, Lactobacillus, and Bifidobacterium) can positively regulate peripheral/vascular leptin level which in turn regulates bone homeostasis via brain serotonin action. htr1b: 5-hydroxytryptamine receptor 1B, PKA: protein kinase A, CREB: cAMP response element-binding protein.