MDM-Pred: a freely available web application for predicting the metabolism of drug-like compounds by the gut microbiota

ABSTRACT

The human gut microbiota (HGM) comprises a complex population of microorganisms that significantly affect human health, including their influence on xenobiotics metabolism. Many pharmaceuticals are taken orally and thus come into contact with HGM, which can metabolize them. Therefore, it is necessary to evaluate the effect of HGM on the fate of pharmaceuticals in the organism. We have collected information about over 600 compounds from more than eighty publications. At least half of them (329 compounds) are known to be metabolized by HGM. We have used PASS (Prediction of Activity Spectra for Substances) software to build three classification SAR models for HGM-mediated drug metabolism prediction. The first model with an accuracy of prediction 0.85 estimates whether compounds will be metabolized by HGM. The second model with an average accuracy of prediction 0.92 estimates which bacterial genera are responsible for the drug metabolism. The third model with an average accuracy of prediction 0.92 estimates the biotransformation reactions during HGM-mediated drug metabolism. The created models were used to develop the freely available web application MDM-Pred (http://www.way2drug.com/mdm-pred/).

KEYWORDS:

• Gut microbiota
• bacterial genus
• microbiota-mediated drug metabolism
• in silico prediction
• SAR
• PASS

Acknowledgements

The study was carried out within the framework of Russian Science Foundation project No. 19-15-00396, https://rscf.ru/project/19-15-00396/.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2023.2214375

Additional information

Funding

This work was supported by the Russian Science Foundation grant No. 19-15-00396.