Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation

Area of Science:

• Microbiology
• Immunology
• Metabolic Diseases

Background:

• Interleukin-18 (IL-18) drives chronic intestinal inflammation.
• Metformin, an anti-diabetic drug, shows promise for inflammatory bowel disease.
• Metformin's mechanism may involve gut microbiota modulation.

Purpose of the Study:

• To investigate the role of gut microbiota in metformin's anti-inflammatory effects.
• To assess the impact of fecal microbiota transplantation (FMT) from metformin-treated mice on host physiology and inflammation.

Main Methods:

• Fecal microbiota transplantation (FMT) from metformin-treated mice to recipient mice.
• Analysis of gene expression, including GLP-1, TLR1, TLR4, and IL-18.
• Gut microbiota composition analysis, focusing on specific genera.

Main Results:

• FMT upregulated GLP-1, TLR1, and TLR4 expression, improving hyperglycemia.
• FMT downregulated the pro-inflammatory cytokine IL-18.
• Metformin-promoted genera Akkermansia, Bacteroides, and Butyricimonas were observed, with Butyricimonas consistently abundant post-FMT.

Conclusions:

• Gut microbiota modulation is central to metformin's anti-inflammatory actions.
• Metformin's effects on hyperglycemia and inflammation are mediated through microbial changes.
• Specific gut bacteria promoted by metformin may contribute to therapeutic benefits.