Vancomycin relieves mycophenolate mofetil–induced gastrointestinal toxicity by eliminating gut bacterial β-glucuronidase activity
Michael R. TaylorAlberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaKyle L. FlanniganDepartment of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaHannah RahimAlberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaAmina MohamudAlberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaIan A. LewisDepartment of Biological Sciences, University of Calgary, Calgary, Alberta, CanadaSimon A. HirotaDepartment of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaSteven C. GreenwayAlberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
2019en
ABI
Аннотация
Mycophenolate mofetil (MMF) is commonly prescribed and has proven advantages over other immunosuppressive drugs. However, frequent gastrointestinal side effects through an unknown mechanism limit its use. We have found that consumption of MMF alters the composition of the gut microbiota, selecting for bacteria expressing the enzyme β-glucuronidase (GUS) and leading to an up-regulation of GUS activity in the gut of mice and symptomatic humans. In the mouse, vancomycin eliminated GUS-expressing bacteria and prevented MMF-induced weight loss and colonic inflammation. Our work provides a mechanism for the toxicity associated with MMF and a future direction for the development of therapeutics.
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