Gut microbiome and orthopaedic health: Bridging the divide between digestion and bone integrity

Figure 1  Mechanisms of bone homeostasis as maintained by a healthy microbiome.

Figure 2 Dysbiosis as a source of inflammation and degeneration through the established gut-bone axis. IFN: Interferon; Ig: Immunoglobulin; IL: Interleukin; MMP: Matrix metalloproteinase; RANKL: Receptor activator of nuclear factor kappa ligand; Th: T-helper; TNF: Tumor necrosis factor.

Figure 3 Mechanism of healthy and dysbiotic microbiome resulting in osteogenesis and osteoclastogenesis respectively. 1 representing transforming growth factor-beta from the healthy microbiome promotes proliferation and early differentiation of bone marrow-derived mesenchymal stromal cells and matrix production. 2 representing interleukin-10 from the healthy microbiome inhibits differentiation and maturation of osteoclasts through upregulation of osteoprotegerin. 3 representing tumor necrosis factor-α from the T cells of dysbiotic microbiome results in the secretion of chemokines by bone marrow-derived mesenchymal stromal cells that increases the recruitment of monocytes into the bone marrow. 4 representing active differentiation of the monocytes into osteoclasts resulting in enhanced bone resorption and osteoclastogenesis. LPS: Lipopolysaccharide; Ig: Immunoglobulin; IL: Interleukin; BM-MSCs: Bone marrow-derived mesenchymal stromal cells; TNF: Tumor necrosis factor; TGF-β: Transforming growth factor-beta; OC: Osteoclast.