The Human Gut Microbiota: A Key Mediator of Osteoporosis and Osteogenesis

Abstract

An expanding body of research asserts that the gut microbiota has a role in bone metabolism and the pathogenesis of osteoporosis. This review considers the human gut microbiota composition and its role in osteoclastogenesis and the bone healing process, specifically in the case of osteoporosis. Although the natural physiologic processes of bone healing and the pathogenesis of osteoporosis and bone disease are now relatively well known, recent literature suggests that a healthy microbiome is tied to bone homeostasis. Nevertheless, the mechanism underlying this connection is still somewhat enigmatic. Based on the literature, a relationship between the microbiome, osteoblasts, osteoclasts, and receptor activator of nuclear factor-kappa-Β ligand (RANKL) is contemplated and explored in this review. Studies have proposed various mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including micro-RNA, insulin-like growth factor 1, and immune system mediation. However, alterations to the gut microbiome secondary to pharmaceutical and surgical interventions cannot be discounted and are discussed in the context of clinical therapeutic consideration. The literature on probiotics and their mechanisms of action is examined in the context of bone healing. The known and hypothesized interactions of common osteoporosis drugs and the human gut microbiome are examined. Since dysbiosis in the gut microbiota can function as a biomarker of bone metabolic activity, it may also be a pharmacological and nutraceutical (i.e., pre- and probiotics) therapeutic target to promote bone homeostasis.

Keywords: bone health; human gut microbiota; microbiome; osteogenesis; osteoporosis; probiotics.

Figure 1

Mechanisms of interaction between the human gut microbiota and bone that lead to increased bone mineral density or suppression of osteoporosis. Created with BioRender.com.

Figure 2

The gut microbiota is only now being recognized as a central regulator of bone homeostasis, particularly after an injury, in what is now being called the gut–bone axis. Many of the regulatory actions are mediated by the microbiota’s metabolic products. Based on this newly recognized microbiota role, bone homeostasis or dysbiosis may be modulated by lifestyle changes, nutraceuticals, or pharmacological agents. Created with BioRender.com.