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Interaction between drugs and the gut microbiome
  1. Rinse K Weersma1,
  2. Alexandra Zhernakova2,
  3. Jingyuan Fu2,3
  1. 1 Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
  2. 2 Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
  3. 3 Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Rinse K Weersma, Gastroenterology and Hepatology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, The Netherlands; r.k.weersma{at}


The human gut microbiome is a complex ecosystem that can mediate the interaction of the human host with their environment. The interaction between gut microbes and commonly used non-antibiotic drugs is complex and bidirectional: gut microbiome composition can be influenced by drugs, but, vice versa, the gut microbiome can also influence an individual’s response to a drug by enzymatically transforming the drug’s structure and altering its bioavailability, bioactivity or toxicity (pharmacomicrobiomics). The gut microbiome can also indirectly impact an individual’s response to immunotherapy in cancer treatment. In this review we discuss the bidirectional interactions between microbes and drugs, describe the changes in gut microbiota induced by commonly used non-antibiotic drugs, and their potential clinical consequences and summarise how the microbiome impacts drug effectiveness and its role in immunotherapy. Understanding how the microbiome metabolises drugs and reduces treatment efficacy will unlock the possibility of modulating the gut microbiome to improve treatment.

  • proton pump inhibition
  • immunotherapy
  • drug metabolism
  • intestinal microbiology

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  • Contributors Conceptualisation and Writing: RKW, AZ and JF.

  • Funding RKW is supported by the Seerave Foundation and the Dutch Digestive Foundation (16-14). AZ is supported by ERC Starting Grant 715772, NWO-VIDI grant 016.178.056 and NWO Gravitation grant Exposome-NL. JF is supported by NWO Gravitation Netherlands Organ-on-Chip Initiative (024.003.001) and the Netherlands Heart Foundation CVON grant 2018-27.

  • Competing interests RKW has received unrestricted Research Grants from Takeda, Johnson & Johnson, Ferring and Tramedico and speakers fees from Abbvie, MSD and Boston Scientific and has acted as a consultant for Takeda Pharmaceuticals.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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