Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss

Area of Science:

• Immunology
• Metabolism
• Bone Biology

Background:

• Microbial metabolites, particularly short-chain fatty acids (SCFAs), influence host immune responses.
• SCFAs are key products of dietary fiber fermentation in the gut and impact both local and systemic immunity.

Purpose of the Study:

• To investigate the role of SCFAs in regulating osteoclast metabolism and bone mass in vivo.
• To determine if SCFA treatment or high-fiber diets can prevent bone loss.

Main Methods:

• Mice were treated with SCFAs or fed a high-fiber diet.
• In vitro and in vivo studies assessed osteoclast differentiation and bone resorption.
• Metabolic analysis identified key pathways affected by SCFAs in osteoclasts.

Main Results:

• SCFA treatment and high-fiber diets significantly increased bone mass in mice.
• SCFAs prevented postmenopausal and inflammation-induced bone loss.
• SCFAs inhibited osteoclast differentiation and bone resorption without affecting bone formation.
• Propionate and butyrate reprogrammed osteoclast metabolism, enhancing glycolysis and downregulating TRAF6 and NFATc1.

Conclusions:

• SCFAs are potent regulators of osteoclast metabolism and bone homeostasis.
• These findings highlight SCFAs as potential therapeutic agents for bone loss conditions.