Impacts of the Human Gut Microbiome on Therapeutics

Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:253-270. doi: 10.1146/annurev-pharmtox-042017-031849. Epub 2017 Oct 2.

Abstract

The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.

Keywords: metabolome; microbial ecology; microbiome; personalized medicine; precision medicine.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cardiac Glycosides / pharmacology
  • Cardiac Glycosides / therapeutic use
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Microbiota / drug effects*
  • Microbiota / physiology*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Cardiac Glycosides