Drug metabolism mapping of the human microbiome by intestinal bacteria and their genes

Drug reactions vary considerably from one individual to another, which can be dangerous and expensive because of treatment delays and side effects. More and more evidence implicates the intestinal microbiome in this variability, but the molecular mechanisms remain largely unknown. Here, we measured the ability of 76 different human intestinal bacteria to metabolize 271 oral drugs and found that many of these drugs were chemically modified by microbes. We have combined high throughput genetics with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes may have a direct and significant impact on the intestinal and systemic metabolism of the drug in mice and may explain the drug metabolizing activities of bacteria and human intestinal communities based on their genomic content. These causal links between microbiota gene content and metabolic activities link the interpersonal variability of the microbiome to the interpersonal differences in drug metabolism, which has implications for medical treatment and drug development in different indications. of illness.