Gut Microbiota and Bone Diseases: A Growing Partnership

Abstract

Gut microbiota is key to human health and disease. Convincing studies have demonstrated that dysbiosis in the commensal gut microbiota is associated with intestinal and extra-intestinal diseases. Recent explorations have significantly contributed to the understanding of the relationship between gut microbiota and bone diseases (osteoporosis, osteoarthritis, rheumatoid arthritis, and bone cancer). Gut microbiota and its metabolites may become associated with the development and progression of bone disorders owing to their critical role in nutrient absorption, immunomodulation, and the gut-brain-bone axis (regulation hormones). In this work, we review the recent developments addressing the effect of gut microbiota modulation on skeletal diseases and explore a feasible preventive approach and therapy for bone diseases.

Keywords: bone diseases; bone tumor; gut microbiota; osteoarthritis; osteoporosis; rheumatoid arthritis.

Figure 1

Schematic representation for the role of gut microbiota in bone health and disease. The potential mechanisms include (1) changes in nutrition absorption (i.e., increase in microbial metabolites with health benefits, such as SCFAs); (2) changes in immunomodulation (i.e., regulation of immune cells and cytokines); (3) regulation of the gut–brain–bone axis (i.e., 5-HT). FMT, fecal microbiota transplantation; SCFAs, short-chain fatty acids; Ca, Calcium; VitD, vitamin D; VitB, vitamin B; VitK, vitamin K; and 5-HT, 5-hydroxytryptamine.

Figure 2

Gut microbial balance (BLUE) vs. gut microbial dysbiosis (RED). When in intestinal homeostasis, gut barrier contributes to surveillance the gut for the entrance of any pathogens. Disruption of the homeostatic relationship between the gut microbiota and gut barrier, the increasing intestinal permeability is involved in further increasing inflammation via gut mucosal immune system, leading to disease.

Figure 3

Potential gut microbiota-related mechanisms in the development of osteoporosis related to the bone remodeling balance including: 1 influencing absorption of nutrition, decreasing in estrogen biotransformation and the level of IGF-1, then regulating bone formation; 2 The GM-dependent expansion of lymphoid cells and cytokines could result in the formation and differentiation of osteoclasts thereby promoting bone destruction; and 3 changing the level of serotonin via the gut–brain–bone axis.