Links Between the Microbiome and Bone

Abstract

The human microbiome has been shown to influence a number of chronic conditions associated with impaired bone mass and bone quality including obesity, diabetes and inflammatory bowel disease. The connection between the microbiome and bone health, however, has not been well studied. The few studies available demonstrate that the microbiome can have a large effect on bone remodeling and bone mass. The gut microbiome is the largest reservoir of microbial organisms in the body and consists of over a thousand different species interacting with one another in a stable dynamic equilibrium. How the microbiome can affect organs distant from the gut is not well understood, but is believed to occur through regulation of nutrition, regulation of the immune system and/or translocation of bacterial products across the gut endothelial barrier. Here we review each of these mechanisms and discuss their potential effect on bone remodeling and bone mass. We review how preclinical studies of bone-microbiome interactions are challenging because the microbiome is sensitive to genetic background, housing environment, and vendor source. Additionally, although the microbiome exhibits a robust response to external stimuli, it rapidly returns to its original steady state after a disturbance, making it difficult to sustain controlled changes in the microbiome over time periods required to detect alterations in bone remodeling, mass or structure. Despite these challenges, an understanding of the mechanisms by which the gut microbiome affects bone has the potential to provide insights into the dissociation between fracture risk and bone mineral density in patients including those with obesity, diabetes or inflammatory bowel disease. In addition, alteration of the gut microbiome has the potential to serve as a biomarker of bone metabolic activity as well as a target for therapies to improve bone structure and quality using pharmaceutical agents or pre- or probiotics.

The Microbiome and Bone and Joint Disease

“…Studies of host-microbe interactions have identified many ways in which changes in the microbiome may influence distant organs, which I classify in three ways: regulation of nutritional absorption, regulation of the immune system at the gut endothelium, and translocation of microbes and molecular products of bacteria across the endothelial barrier and into the systemic circulation (Fig 1) [11]. …”

“…Many clinical conditions that are associated with or contribute to the development of osteoporosis are also associated with changes in the gut microbiota [11]. However, to date there is only one report linking the microbiome to osteoporosis in humans: the gut flora in patients with osteoporosis (defined using bone mineral density (BMD)) was recently reported to be different from that of normal controls (microbiota assessed by analysis of fecal 16S rRNA) [28].…”

“…Three primary methods have been used to demonstrate an effect of the microbiome on bone: examination of germ-free mice, chronic treatment with oral antibiotics to manipulate the gut flora, and treatment with probiotics [11]. Germ free mice are raised in sterile incubators and are never exposed to live microbes in their life (MAMPs and dead bacteria may be present in the sterilized food and water provided to the animals).…”

Safety and risk assessment for the human superorganism

“…Besides the fact that human microbes encounter environmental agents via inhaled, oral, or dermal routes before our own mammalian cells, the microbes also respond to external agents. This impacts the status of the microbiome, which in turn affects the host brain and neurological system (Dinan and Cryan 2016), gut (Imhann et al 2016), liver (Selwyn et al 2016), bone (Hernandez et al 2016), kidney (Pluznick 2016), endocrine organs and tissues (Kunc et al 2016), reproductive system (Nelson et al 2016), and immune system and host defense (Levy et al 2016;Brown and Clark 2017). Figure 1.…”

The Microbiome: Current and Future view of an Ancient Paradigm

“…Wide health claims are made for both, but more work defining specific molecular mechanisms is needed. Using the example of bone health, modification (or restitution) of the gut microbiota via nutritional supplementation with prebiotics and probiotics appear to be a new promising therapeutic strategy for osteoporosis [9,17,18]. In theory, identification of taxa with specific cell biological or immunomodulatory activities could be candidates for potential probiotic supplementation to address multiple conditions.…”