Research by Angel J. Ruiz-Moreno and Jingyuan Fu developed a novel tool to predict chemical transformation that can be made by human and bacterial enzymes. The tool employed 13,540 human reactions and 8,638 unique microbial reactions from over 6,000 strains. When applied to over 1,000 orally administrated drugs, the study predicts drugs that can be either metabolized by human, gut microbes or both. The results were published in Microbiome yesterday

Gut microorganisms play a crucial role in human health, particularly through their ability to metabolize dietary compounds and xenobiotics, which directly impact nutrition, drug response, and disease risk. While advances in genomic analysis have provided insights into the types of enzymes these microbes carry, there is still limited knowledge about the metabolites they produce. MicrobeRX, developed by Ruiz-Moreno et al., addresses this gap by generating over 68,000 chemical reaction rules, mapping substrate-enzyme-product relationships for both human and microbial transformations. This tool enhances our understanding of microbiome-driven metabolism and its implications for health and therapeutics.

The study by Ruiz-Moreno et al. demonstrated the significant role of gut microbes in drug metabolism by predicting that 526 drugs undergo biotransformation by both human and microbial enzymes, while 102 drugs are metabolized exclusively by human enzymes and 106 solely by gut microbes. These findings highlight the intricate interplay between host and microbial metabolism, which can influence drug efficacy, response variability, and potential toxicity. Understanding these interactions is crucial for optimizing drug design, minimizing adverse effects, and personalizing treatment strategies.

MicrobeRX bridges the gap between genomic data and chemical transformations by generating over 68,000 reaction rules that map substrate-enzyme-product relationships for both human and microbial metabolism. This comprehensive approach enables researchers to explore the metabolic capabilities of gut microbes beyond just enzyme presence, offering new insights into their role in human health. With applications spanning precision medicine, drug discovery, nutrition, the food and pharmaceutical industries, and environmental safety, MicrobeRX provides a valuable framework for harnessing the chemical potential of the gut microbiome.

This study was funded by the ERC Consolidator Grant awarded to Jingyuan Fu, supporting research focused on harnessing the gut microbiome to enhance drug efficacy. The grant aims to deepen our understanding of microbial contributions to drug metabolism, paving the way for microbiome-targeted therapeutic strategies. By integrating microbiome research with drug development, this initiative seeks to optimize treatment outcomes, reduce adverse drug reactions, and advance precision medicine.

Source: https://umcgresearch.org/w/novel-tool-to-predict-biotransformation-by-our-gut-microbes