Microbial activation of the GLP-2R mitigates gastrointestinal inflammation

Area of Science:

• Microbiology
• Immunology
• Nutritional Science

Background:

• Growing global demand for sustainable protein sources.
• Need for novel dietary strategies to manage gastrointestinal inflammation.

Purpose of the Study:

• To investigate the potential of microbial lysates, specifically Methylococcus capsulatus Bath (McB), as a sustainable dietary protein.
• To elucidate the mechanisms by which McB impacts host-diet-microbe interactions and protects against gastrointestinal inflammation.

Main Methods:

• Administration of commercially scalable microbial lysate (McB) in preclinical models.
• Analysis of gut microbiota composition and function.
• Assessment of immune cell populations, including regulatory T cells (pTregs) and tolerogenic Th17 cells.
• Evaluation of intestinal villus architecture and mucosal integrity.
• Investigation of GLP-2 receptor signalling pathways.

Main Results:

• McB rapidly altered gut microbiota composition and upregulated microbial fermentation pathways.
• McB robustly increased peripherally induced regulatory T cells (pTregs) independently of the microbiota.
• McB-induced tolerogenic Th17 cells required a functional microbiota with intact fermentation capacity.
• McB administration preserved villus architecture, restored mucosal integrity, and reduced disease severity in models of mucositis and colitis.
• The protective effects were dependent on microbial fermentation and GLP-2 receptor signalling, mimicking GLP-2R activation.

Conclusions:

• Microbial lysates, such as McB, represent a sustainable nutritional strategy for improving gastrointestinal health.
• McB exerts protective effects through distinct immune and microbial pathways, including fermentation-driven GLP-2R activation.
• These findings highlight the therapeutic potential of microbial lysates in managing inflammatory conditions of the gut.