Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.
Moataz E Mohamed, Abdelrahman Saqr, Christopher Staley, Guillaume Onyeaghala, Levi Teigen, Casey R Dorr, Rory P Remmel, Weihua Guan, William S Oetting, Arthur J Matas, Ajay K Israni, Pamala A Jacobson
Author Information
Moataz E Mohamed: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN.
Abdelrahman Saqr: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN.
Christopher Staley: Department of Surgery, University of Minnesota, Minneapolis, MN.
Guillaume Onyeaghala: Hennepin Healthcare Research Institute, Minneapolis, MN.
Levi Teigen: Department of Food Science and Nutrition, University of Minnesota, St Paul, MN.
Casey R Dorr: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN.
Rory P Remmel: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN.
Weihua Guan: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN.
William S Oetting: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN.
Arthur J Matas: Department of Surgery, University of Minnesota, Minneapolis, MN.
Ajay K Israni: Hennepin Healthcare Research Institute, Minneapolis, MN.
Pamala A Jacobson: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN.
The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.
References
Eur J Drug Metab Pharmacokinet. 1997 Jul-Sep;22(3):217-21
[PMID: 9358202]
