Metformin as a Metabolic Reprogramming Interface in Host-Pathogen and Bone Microenvironment Crosstalk: A Dual-Target...

Area of Science:

• Integrative biology
• Metabolic pathways
• Host-pathogen interactions

Background:

• Metabolic dysregulation is central to chronic infection, immune dysfunction, and bone deterioration.
• These interconnected processes are often studied in isolation, hindering integrated understanding.
• A systems-level framework is needed to bridge host-pathogen dynamics and bone remodeling.

Purpose of the Study:

• Propose the Metabolic Reprogramming Interface Model (MRIM) as a hypothesis-generating construct.
• Conceptualize metabolism as a shared axis linking host-pathogen interactions and bone remodeling.
• Organize and evaluate multidisciplinary evidence on metabolic influence.

Main Methods:

• Review and synthesis of existing literature.
• Conceptual framework development (MRIM).
• Analysis of molecular mechanisms of metformin (AMPK, mitochondria, redox, autophagy).

Main Results:

• MRIM integrates evidence suggesting metabolic perturbations influence infection, inflammation, and bone turnover.
• Metformin's known effects on cellular metabolism are implicated in microbial persistence, immune function, and skeletal homeostasis.
• Current evidence is largely indirect, requiring further validation.

Conclusions:

• Metabolic reprogramming is a key interface in chronic infection and bone health.
• MRIM provides a scaffold for interdisciplinary research, not a definitive model.
• Further clinical trials are needed to validate metformin's effects on combined infectious and skeletal outcomes.