A Functional Metabolomics Framework to Track Microbiome Drug Metabolism.

Area of Science:

• Microbiology
• Pharmacology
• Metabolomics

Background:

• Gut microbes significantly impact drug efficacy and side effects by transforming pharmaceuticals.
• Discovering these microbiome-derived drug metabolites is crucial for drug development and personalized medicine.
• Current methods for identifying drug metabolites in complex microbial environments are limited.

Purpose of the Study:

• To develop and validate a functional metabolomics workflow for accelerated discovery of microbiome-derived drug metabolites.
• To investigate chemical transformation dynamics of clinical drugs within a synthetic gut microbial community.
• To establish links between microbial community composition and drug biotransformation processes.

Main Methods:

• Utilized synthetic microbial communities (SynComs) to model gut microbial drug metabolism.
• Employed time-series resolved molecular networking for comprehensive metabolite profiling.
• Integrated advanced computational tools for accurate metabolite annotation and analysis.

Main Results:

• Identified a multitude of drug metabolites, including complex multi-step metabolic cascades.
• Observed correlations between specific drug metabolites and shifts in microbial taxa within the SynCom.
• Demonstrated the framework's capability to illuminate drug transformation dynamics in a 50-drug panel.

Conclusions:

• The developed functional metabolomics workflow effectively accelerates the discovery of drug metabolites produced by gut microbes.
• Findings suggest functional links between gut microbiome composition and drug biotransformation, impacting pharmaceutical outcomes.
• The computational analysis workflow is publicly available, facilitating broader research in biotransformation and chemical ecology.