Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases

Abstract

The extended microbial genome-the gut microbiome (GM)-plays a significant role in host health and disease. It is able to influence a number of physiological functions. During dysbiosis, GM is associated with the development of various chronic diseases with impaired bone quality. In general, GM is important for bone homeostasis and can affect it via several mechanisms. This review describes the roles of GM in bone homeostasis through influencing the immune and endocrine functions, short-chain fatty acids production, calcium absorption and the gut-brain axis. The relationship between GM composition and several bone-related diseases, specifically osteoporosis, osteoarthritis, rheumatoid arthritis, diabetes mellitus, obesity and bone cancer, is also highlighted and summarized. GM manipulation may become a future adjuvant therapy in the prevention of many chronic diseases. Therefore, the beneficial effects of probiotic therapy to improve the health status of individuals with aforementioned diseases are provided, but further studies are needed to clearly confirm its effectiveness. Recent evidence suggests that GM is responsible for direct and indirect effects on drug efficacy. Accordingly, various GM alterations and interactions related to the treatment of bone-related diseases are mentioned as well.

Keywords: bone cancer; bone homeostasis; diabetes mellitus; gut microbiome; obesity; osteoarthritis; osteoporosis; pharmacological drugs; probiotic therapy; rheumatoid arthritis.

Figure 1

The GM has various roles in the host organism. It can affect various physiological roles, such as fermentation of complex carbohydrates [24], immune system [25], synthesis of neuroactive compounds [26], vitamin synthesis [27] and bile acid metabolism [28]. It can also affect many pathophysiological (during dysbiosis) roles [7]. (Created with BioRender.com).

Figure 2

Lymphocytes can regulate bone remodeling through the expression of cytokines, as well as RANKL and OPG. (Created with BioRender.com).

Figure 3

Mice lacking GM exhibited increased trabecular BMD, which was associated with decreased OCs, CD4⁺ T cells and OC precursor cells and lowered TNFα and IL-6 expression [40]. T cells are known to secrete osteoclastogenic cytokines such as TNF- α and IL-6 [41]. Intestinal bacteria are needed to develop the immune system. In GF mice, the mucosal immune system is undeveloped, having reduced the lamina propria CD4⁺ T cells. Moreover, the spleen and lymph nodes are also affected, as they are relatively structureless with poorly formed B- and T-cell zones [42]. (Created with BioRender.com).