High-fat diet disrupts REG3γ and gut microbial rhythms promoting metabolic dysfunction

Area of Science:

• Microbiology
• Metabolism
• Chronobiology

Background:

• Gut microbial diurnal oscillations are crucial for host circadian rhythms and metabolism.
• The complex interplay between diet, microbes, and host factors regulating intestinal oscillations is not fully understood.

Purpose of the Study:

• To investigate the role of host C-type lectin antimicrobial peptide Reg3γ in orchestrating diet-microbe-host interactions in the gut.
• To understand how high-fat diets disrupt microbial oscillations and impact host metabolic homeostasis.

Main Methods:

• Utilized a mouse model to study gut microbial and host factor dynamics.
• Analyzed the relationship between diet, host Reg3γ expression, and gut microbial oscillations.

Main Results:

• Host Reg3γ peptide and specific ileal microbes bidirectionally orchestrate gut rhythms independently of the core circadian clock.
• High-fat diets primarily drive microbial oscillations that impair host metabolic homeostasis.
• Arrhythmic host Reg3γ expression, driven by high-fat diets, secondarily affects microbial abundance and oscillations.

Conclusions:

• Transkingdom coordination of biological rhythms is significantly influenced by diet and reciprocal host-microbial signals.
• Restoring the gut microbiota's ability to sense dietary signals via host factors like Reg3γ may improve metabolic dysfunction.