Role of the microbiome in regulating bone metabolism and susceptibility to osteoporosis

The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.