Gut microbiota preserves bone mass through modulating the hyodeoxycholic acid-TGR5 axis.

Area of Science:

• Microbiology
• Metabolomics
• Bone Biology

Background:

• Osteoporosis is an age-related condition.
• The link between gut microbiota (GM) and bone health is known, but mechanisms of GM dysbiosis in senile osteoporosis are unclear.
• This study investigates GM, bile acids (BAs), and their impact on bone mass.

Purpose of the Study:

• To elucidate the relationship between gut microbiota, bile acids, and bone mass.
• To identify specific microbial and metabolic factors contributing to age-related bone loss.
• To explore potential therapeutic targets for osteoporosis.

Main Methods:

• 16S rRNA sequencing for microbial analysis.
• Untargeted and targeted metabolomics for bile acid profiling.
• In vitro and in vivo experiments involving mouse models and cell cultures.

Main Results:

• Reduced microbial diversity and altered bile acid profiles were observed in old mice.
• A decrease in *Parabacteroides goldsteinii* and hyodeoxycholic acid (HDCA) correlated with reduced bone mass.
• Gut microbiota transplantation from young to old mice preserved bone mass by inhibiting bone resorption.
• HDCA protected bone by activating the TGR5 receptor, inhibiting osteoclast maturation and P65 nuclear translocation.

Conclusions:

• The gut microbiota-HDCA-TGR5 axis is a critical pathway influencing bone mass.
• Targeted intervention with HDCA shows promise as a therapeutic strategy for osteoporosis.