Estrogen deficiency induces bone loss through the gut microbiota

Area of Science:

• Metabolic bone disease research
• Microbiome and host interactions
• Gut microbiota and osteoporosis

Background:

• Postmenopausal osteoporosis is a prevalent metabolic bone disease.
• Gut microbiota (GM) dysbiosis is implicated in metabolic bone disease development.
• Ovariectomized mice exhibit increased serum lipopolysaccharide and altered gut microbiota composition.

Purpose of the Study:

• To investigate the role of gut microbiota in postmenopausal osteoporosis.
• To explore the therapeutic potential of targeting gut microbiota and TGR5 in osteoporosis.

Main Methods:

• Ovariectomized mouse model.
• Antibiotic-induced gut microbiota depletion.
• Gut microbiota transplantation.
• Bone histomorphometry and biomechanical testing.
• Gene expression analysis and TGR5 manipulation (siRNA, knockout).

Main Results:

• Gut microbiota depletion improved bone mass, microstructure, and strength in ovariectomized mice.
• Transplantation of ovariectomy-adapted GM induced bone loss.
• GM depletion reversed ovariectomy-induced tibial gene expression changes and increased bone formation.
• TGR5 plays a key role in mediating GM-induced bone loss.

Conclusions:

• Gut microbiota critically contributes to bone loss in postmenopausal osteoporosis.
• Targeting the G-protein-coupled bile acid receptor TGR5 within the gut microbiota may represent a novel therapeutic strategy for postmenopausal osteoporosis.