From Osteoimmunology to Osteomicrobiology: How the Microbiota and the Immune System Regulate Bone

Abstract

Osteomicrobiology refers to the role of microbiota in bone health and the mechanisms by which the microbiota regulates post-natal skeletal development, bone aging, and pathologic bone loss. Here, we review recent reports linking gut microbiota to changes in bone phenotype. A pro-inflammatory cytokine milieu drives bone resorption in conditions such as sex steroid hormone deficiency. The response of the immune system to activation by the microbiome results in increased circulating osteoclastogenic cytokines in a T cell-dependent mechanism. Additionally, gut microbiota affect bone homeostasis through nutrient absorption, mediation of the IGF-1 pathway, and short chain fatty acid and metabolic products. Manipulation of microbiota through prebiotics or probiotics reduces inflammatory cytokine production, leading to changes in bone density. One mechanism of probiotic action is through upregulating tight junction proteins, increasing the strength of the gut epithelial layer, and leading to less antigen presentation and less activation of intestinal immune cells. Thus, prebiotics or probiotics may represent a future therapeutic avenue for ameliorating the risk of postmenopausal bone loss in humans.

Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo‐controlled, double‐blind, clinical trial

“…Older women are at a very high risk for fragility fractures , and to substantially reduce the yearly bone loss in this group of patients using a naturally occurring bacteria is a new concept which could lead to a paradigm shift in the prevention of osteoporosis. Previous studies in rodents have suggested that treatment with specific bacterial strains can improve bone density but the present study demonstrates for the first time that this may also be the case in humans.…”

Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging

“…Several studies have also shown a clear link between Toll‐like receptor signaling by the microbiome and ISC Wnt signaling . Thus, an abnormal microbiome may disrupt ISC Wnt signaling required to maintain normal intestinal crypt cell fate and barrier function and may be a critical cause of inflammaging resulting in aging‐associated bone loss, as seen in the ovarectomized mouse model …”

“…120 Much recent interest in bone metabolism, especially in aging, has focused on the role of the intestinal tract, especially the role of dysregulated intestinal epithelial barrier function, resulting in hyperpermeability (leaky gut), and the intestinal microbiome. 121 Leaky gut increases with aging in species from Drosophila to humans, [122][123][124] and can promote systemic inflammation via lipopolysaccharide and other microbial products. 125 Several studies have shown significant effects of the microbiome on bone health, resulting in a new area of study termed osteomicrobiology.…”

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

“…It is now clear that changes in the gut microbiota can impact bone density and health . For example, intestinal infection with pathogenic bacteria can induce bone loss in male mice .…”