Macrophage-Orchestrated Metabolic Sensing Drives IBD Pathogenesis: A Framework for Targeted Therapy.

Area of Science:

• Immunology
• Gastroenterology
• Metabolism

Background:

• Inflammatory bowel disease (IBD) involves complex interactions between gut microbiota, the immune system, and the intestinal epithelium.
• Intestinal macrophages play a critical role but are often seen as mere inflammatory effectors.

Purpose of the Study:

• To reframe intestinal macrophages as central metabolic sensors and regulatory hubs in IBD.
• To introduce the Macrophage-Orchestrated Metabolic Sensor (MOMS) framework.

Main Methods:

• Conceptual review integrating evidence from immunometabolism, microbiome research, and single-cell biology.
• Identification of key molecular regulators like METTL3 and NLRP3.

Main Results:

• The MOMS framework proposes three layers: Sense (metabolite detection), Switch (metabolic/epigenetic reprogramming), and Command (driving tissue responses).
• Key molecular nodes (METTL3, NLRP3) are identified as regulators of macrophage fate.

Conclusions:

• The MOMS framework provides a new perspective on macrophage function in IBD.
• This framework generates testable predictions and supports the development of precision macrophage-directed therapies for immune-metabolic disorders.