Targeting gut-derived NETosis: A paradigm shift in understanding metformin's therapeutic action

Area of Science:

• Immunology
• Gastroenterology
• Pharmacology

Background:

• Metformin is a primary diabetes drug with incompletely understood mechanisms.
• The intestine plays a key role in metformin's effects, involving microbiota, epithelial cells, and immunity.
• Metformin has immunomodulatory activity, affecting neutrophil function and NETosis.

Purpose of the Study:

• To explore intestinal neutrophil extracellular trap formation (NETosis) as a novel therapeutic target of metformin.
• To review the potential therapeutic relevance of targeting intestinal NETosis for diabetes management.

Main Methods:

• Literature review of studies on metformin, gut microbiota, immune system, and NETosis in diabetes.
• Analysis of emerging evidence linking intestinal NETosis to metabolic dysregulation and diabetes complications.

Main Results:

• Excessive NETosis is associated with diabetes and its complications.
• Gut microbiota alterations influence NETosis, which may contribute to metabolic dysfunction.
• Intestinal NETosis is a potential mechanism through which metformin exerts therapeutic effects.

Conclusions:

• Intestinal NETosis represents a promising, yet under-investigated, target for metformin therapy.
• Understanding these pathways can inform personalized therapies and next-generation diabetes drugs.
• Further research is crucial to elucidate metformin's impact on intestinal NETosis and its therapeutic potential.