Bone Remodeling and the Microbiome

Abstract

Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the microbiome. The gastrointestinal tract harbors the greatest numbers of these microorganisms, which regulate human nutrition, metabolism, and immune system function. Moreover, the intestinal microbiota contains pro- and anti-inflammatory products that modulate immune responses and may play a role in maintaining gut barrier function. Therefore, the community composition of the microbiota has profound effects on the immune status of the host and impacts the development and/or progression of inflammatory diseases. Accordingly, numerous studies have shown differences in the microbiota of patients with and without a given inflammatory condition. There is now strong evidence that the gut microbiome regulates bone homeostasis in health and disease, and that prebiotic and probiotics protect against bone loss. Herein, the evidence supporting the role of the microbiota and the effects of prebiotic and probiotics will be reviewed.

Figure 1.

Germ-free (GF) mice are protected against the loss of trabecular bone induced by sex steroid deficiency. Three-dimensional reconstructions of femoral bone by in vitro microcomputed tomography in conventionally raised (Conv. R) mice, GF mice, and colonized GF (Col. GF) mice following treatment with the gonadotrophin-releasing hormone (GN-RH) agonist leuprolide (Leu) or vehicle control for 10 weeks. The images show that GF mice are protected against the loss of trabecular bone induced by sex steroid deficiency. (From Gao et al. 2007; reproduced, with permission, from the Journal of Clinical Investigation © 2007.)

Figure 2.

Diagrammatic representation of the effects of sex steroid deficiency on gut permeability. In physiologic conditions, proteins of the JAMs and claudin family seal the space between intestinal epithelial cells preventing bacteria and bacterial products from penetrating the intestinal wall and activating immune cells. Sex steroid deprivation down-regulates the expression of gap junction proteins, leading to increased gut permeability. The resulting increased bacterial translocation induces a local and systemic immune response that causes an increased production of osteoclastogenic cytokines. Probiotic supplementation up-regulates expression of claudins and JAMs, thus restoring normal gut barrier function.

Figure 3.

Probiotic supplementation prevents sex steroid–induced bone loss. Conventional ovariectomized (ovx) and sham-operated mice were supplemented twice a week with VSL#3, Lactobacillus rhamnosus GG (LGG), or vehicle (veh.). The figure shows in vivo prospective measurements of spinal bone volume (BV/TV), as measured by microcomputed tomography (μCT) scanning at baseline and 2 and 4 weeks after surgery. n = 10–14 mice per group. Data are expressed as mean ± SEM. a = p < 0.05, b = p < 0.01, and c = p < 0.001 compared with baseline. *p < 0.05 and ***p < 0.001 compared with sham vehicle. (From Cenci et al. 2000; reproduced, with permission, from the Journal of Clinical Investigation © 2000.)