In vivo mechanism of the interaction between trimethylamine lyase expression and glycolytic pathways

Area of Science:

• Microbiology
• Metabolomics
• Host-Microbiota Interactions

Background:

• Host-gut microbiota interactions influence disease-linked metabolite trimethylamine (TMA) production via TMA lyase.
• Mechanisms regulating microbial enzyme production, particularly TMA lyase, remain incompletely understood.

Purpose of the Study:

• To investigate how dietary and intervention factors affect gut microbiota, gene expression, and the interplay between TMA lyase and glycolytic pathways in mice.
• To elucidate the regulatory mechanisms controlling TMA production in the gut.

Main Methods:

• Utilized 16S rRNA gene sequencing, metagenomics, and metabolomics to analyze gut microbiota composition and functional gene expression.
• Assessed microbial gene expression profiles related to TMA lyase and glycolytic enzymes in response to dietary and intervention changes.

Main Results:

• Distinct diets and interventions significantly altered gut microbiota composition, gene expression, and metabolites associated with glycine metabolism and glycolysis.
• An arabinoxylan-rich diet suppressed genes involved in choline, glycine, glycolysis, and TMA lyase, promoting glycine utilization through pyruvate pathways.
• Glycolytic inhibitors, particularly those targeting pyruvate kinase, amplified the observed effects on gene expression and metabolite profiles.

Conclusions:

• Demonstrated a significant crosstalk between TMA lyase and glycolytic pathways in regulating glycine levels within the gut microbiota.
• Findings suggest that targeted interventions and personalized dietary approaches, such as incorporating arabinoxylan-rich foods, can effectively modulate TMA lyase production.
• Highlights potential strategies for managing TMA-related health risks through dietary manipulation and understanding microbial metabolic pathways.