Dozens of drugs are known to be metabolized by the human gut microbiome. However, the influence of bacterial metabolism on drug efficacy is only beginning to be understood. In a recent study involving Dr’s MacNeil, Surette, Wright, and past and current IIDR trainees, a collection of gut isolates were screened for their ability to inactivate the widely used antineoplastic drug doxorubicin, identifying a strain of Raoultella planticola. This strain was identified as a potent inactivator under anaerobic conditions, using a novel mechanism of degradation dependent on molybdopterin-dependent enzyme(s). Degradation of doxorubicin by R. planticola was found to reduce toxicity of the drug to the model species Caenorhabditis elegans, providing a model to begin understanding the role of doxorubicin metabolism by microbes in the human gut. Understanding the in vivo metabolism of important therapeutics like doxorubicin by the gut microbiome has the potential to guide clinical dosing to maximize therapeutic benefit while limiting undesirable side effects.
Read the full publication in ACS Infectious Diseases.