Human and animal studies have implicated the microbiome as a regulator of bone mass in health and disease. For example, a recent human study has described the first evidence of a correlation between microbiome diversity and osteoporosis, while another has shown that subjects with high bone density have fewer Bacteroidetes and more abundant Firmicutes.
Animal studies have disclosed that C57BL/6 mice raised in a germ-free (GF) environment, have a higher bone mass than controls raised in conventional housing, due to lower production of osteoclastogenic cytokines by antigen-activated immune cells. By contrast, BALB/c and CBSF1 mice raised in conventional conditions have a higher bone density than those raised in GF conditions, implying that the microbiota impact on skeletal homeostasis is in part regulated by mouse strain genetic determinants.
The microbiome is also relevant for the skeletal response to pathological conditions. For example, we showed that the presence of the microbiota is required for estrogen deficiency to cause bone loss. Estrogen deficiency does not change the composition of the microbiota but increases gut permeability allowing the gut microbiota to induce T cell activation and cytokine release in the gut and then in the BM. It is also known that antibiotic treatment increases bone density in mice and prevents ovariectomy-induced bone loss, while bacterial recolonization post-antibiotic treatment causes bone loss. Alterations of the microbiome affect not only bone mineral density but also bone strength via an effect on changes in bone tissue material properties. Multiple mechanisms explain how the microbiome affects bone.
Translocation of bacterial products (e.g. LPS and flagellin) across the intestinal barrier, and their systemic spread via the bloodstream is one mechanism whereby the microbiota may cause inflammation and bone loss. In addition, the response of the gut immune system to the microbiome results in the local activation of immune cells and the production of a variety of cytokines (e.g. IIL-6, IL-17, TNF, and RANKL) . Accordingly, we found that gut microbiota influences systemic immune responses critical for bone loss induced by sex steroid deficiency.
Interest in the field of osteomicrobiology is growing, as typified by the recent workshop on the role of the microbiome in regulating bone metabolism and susceptibility to osteoporosis held by the Royal Osteoporosis Society. As in this workshop, this collection aims to outline the key clinical areas for novel research to advance our understanding of this relationship, including methodological suggestions and priority research agendas.
This article collection will include basic, translational, epidemiological, original research articles and reviews from human, animal and in vitro studies to help to understand the novel mechanism by which the gut microbiota impacts skeletal homeostasis and. This will hopefully lead to advancements in identifying new drug targets for the treatment of bone diseases.
Themes of interest include, but are not limited to:
• Studies on the relationship between intestinal microflora and bone loss;
• Recent advances in the interactions of the gut microbiota, immune responses and the downstream effects on regulating bone mass;
• Antibiotics, probiotics and other gut microbiome-targeted strategies in the prevention and treatment of bone loss
• The mechanisms by which modern lifestyle, diet and illness exert their effects on bone health via the gut microbiome.
Human and animal studies have implicated the microbiome as a regulator of bone mass in health and disease. For example, a recent human study has described the first evidence of a correlation between microbiome diversity and osteoporosis, while another has shown that subjects with high bone density have fewer Bacteroidetes and more abundant Firmicutes.
Animal studies have disclosed that C57BL/6 mice raised in a germ-free (GF) environment, have a higher bone mass than controls raised in conventional housing, due to lower production of osteoclastogenic cytokines by antigen-activated immune cells. By contrast, BALB/c and CBSF1 mice raised in conventional conditions have a higher bone density than those raised in GF conditions, implying that the microbiota impact on skeletal homeostasis is in part regulated by mouse strain genetic determinants.
The microbiome is also relevant for the skeletal response to pathological conditions. For example, we showed that the presence of the microbiota is required for estrogen deficiency to cause bone loss. Estrogen deficiency does not change the composition of the microbiota but increases gut permeability allowing the gut microbiota to induce T cell activation and cytokine release in the gut and then in the BM. It is also known that antibiotic treatment increases bone density in mice and prevents ovariectomy-induced bone loss, while bacterial recolonization post-antibiotic treatment causes bone loss. Alterations of the microbiome affect not only bone mineral density but also bone strength via an effect on changes in bone tissue material properties. Multiple mechanisms explain how the microbiome affects bone.
Translocation of bacterial products (e.g. LPS and flagellin) across the intestinal barrier, and their systemic spread via the bloodstream is one mechanism whereby the microbiota may cause inflammation and bone loss. In addition, the response of the gut immune system to the microbiome results in the local activation of immune cells and the production of a variety of cytokines (e.g. IIL-6, IL-17, TNF, and RANKL) . Accordingly, we found that gut microbiota influences systemic immune responses critical for bone loss induced by sex steroid deficiency.
Interest in the field of osteomicrobiology is growing, as typified by the recent workshop on the role of the microbiome in regulating bone metabolism and susceptibility to osteoporosis held by the Royal Osteoporosis Society. As in this workshop, this collection aims to outline the key clinical areas for novel research to advance our understanding of this relationship, including methodological suggestions and priority research agendas.
This article collection will include basic, translational, epidemiological, original research articles and reviews from human, animal and in vitro studies to help to understand the novel mechanism by which the gut microbiota impacts skeletal homeostasis and. This will hopefully lead to advancements in identifying new drug targets for the treatment of bone diseases.
Themes of interest include, but are not limited to:
• Studies on the relationship between intestinal microflora and bone loss;
• Recent advances in the interactions of the gut microbiota, immune responses and the downstream effects on regulating bone mass;
• Antibiotics, probiotics and other gut microbiome-targeted strategies in the prevention and treatment of bone loss
• The mechanisms by which modern lifestyle, diet and illness exert their effects on bone health via the gut microbiome.
