A microbiome-dependent gut-bone axis determines skeletal benefits from mechanical loading

Area of Science:

• Microbiology
• Bone Physiology
• Metabolism

Background:

• Bone mechanical adaptation exhibits significant inter-individual variability.
• The gut microbiota's role in regulating bone health is increasingly recognized.
• Arginine metabolism is crucial for various physiological processes, including bone remodeling.

Purpose of the Study:

• To investigate the link between gut microbial alterations in arginine metabolism and bone mechanical adaptation.
• To elucidate the mechanisms by which gut microbiota influence bone mechanoresponsiveness.
• To identify potential microbial targets for enhancing bone health and preventing osteoporosis.

Main Methods:

• Administration of L-arginine and specific gut bacteria (Lachnospiraceae) to model systems.
• Analysis of bone mechanical properties and mechanoresponsiveness.
• Assessment of nitric oxide and calcium signaling pathways in osteocytes.
• Microbiota composition analysis to identify key bacterial families.

Main Results:

• L-arginine administration enhanced bone mechanical adaptation via a nitric oxide-calcium feedback loop in osteocytes.
• Significant differences in gut microbiota composition, particularly Lachnospiraceae, were associated with inter-individual variability in bone mechanoresponsiveness.
• Administration of Lachnospiraceae increased L-citrulline and L-arginine levels and improved bone mechanoresponsiveness.

Conclusions:

• Gut microbiota composition, specifically Lachnospiraceae, significantly impacts bone mechanical adaptation.
• The microbiota-metabolite axis, involving arginine metabolism, represents a novel therapeutic target for enhancing bone mechanoresponsiveness.
• These findings offer a potential preventive and therapeutic strategy for osteoporosis by modulating the gut microbiota.