Abstract
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.
Highlights
This viewpoint article summarizes current knowledge in the microbiome field and identifies research priorities to advance microbiome research in osteoporosis and bone health
The overall goal is to improve our current understanding of the relationship between the microbiome and bone health, and to translate this knowledge into actionable recommendations to prevent the development of osteoporosis or to find a cure for patients with this condition
This study provides an excellent example of how metagenomic sequencing, combined with metabolite quantification in biological samples, can provide valuable insight into functional metabolic capacity and activity, allowing us to understand how the gut microbiome can affect processes relevant to bone health
Summary
This viewpoint article summarizes current knowledge in the microbiome field and identifies research priorities to advance microbiome research in osteoporosis and bone health. Nissen and colleagues performed a double-blind, placebo-controlled trial examining the effect of the probiotic Lactobacillus reuteri ATCC PTA 6475 on bone loss of women with reduced bone mass (mean age 76 years) [18] This trial built upon convincing evidence from ovariectomized mice, where supplementation with L. reuteri ATCC PTA 6475 protected against bone resorption and loss associated with oestrogen deficiency [52]. The effects of Lactobacilli probiotics for improvement of bone health was further studied using a combination of three Lactobacillus strains (L. paracasei DSM 13434, L. plantarum DSM 15312, and L. plantarum DSM 15313) in a multicentre, randomized, double-blind, placebo-controlled trial in Sweden [19] This trial built on evidence in ovariectomized mice, where supplementation with the same mix of three Lactobacillus strains protected against bone loss associated with oestrogen deficiency [54]. IBD inflammatory bowel disease, IBS irritable bowel syndrome, JIA juvenile idiopathic arthritis, BMD bone mineral density, PBM peak bone mass, DASH dietary approaches to stopping hypertension the importance of advancing our knowledge of the impact of early life on development of the gut microbiome in relation to bone health
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