Mirror, mirror on the wall: which microbiomes will help heal them all?

Abstract

Background: Clinicians have known for centuries that there is substantial variability between patients in their response to medications-some individuals exhibit a miraculous recovery while others fail to respond at all. Still others experience dangerous side effects. The hunt for the factors responsible for this variation has been aided by the ability to sequence the human genome, but this just provides part of the picture. Here, we discuss the emerging field of study focused on the human microbiome and how it may help to better predict drug response and improve the treatment of human disease.

Discussion: Various clinical disciplines characterize drug response using either continuous or categorical descriptors that are then correlated to environmental and genetic risk factors. However, these approaches typically ignore the microbiome, which can directly metabolize drugs into downstream metabolites with altered activity, clearance, and/or toxicity. Variations in the ability of each individual's microbiome to metabolize drugs may be an underappreciated source of differences in clinical response. Complementary studies in humans and animal models are necessary to elucidate the mechanisms responsible and to test the feasibility of identifying microbiome-based biomarkers of treatment outcomes. We propose that the predictive power of genetic testing could be improved by taking a more comprehensive view of human genetics that encompasses our human and microbial genomes. Furthermore, unlike the human genome, the microbiome is rapidly altered by diet, pharmaceuticals, and other interventions, providing the potential to improve patient care by re-shaping our associated microbial communities.

Keywords: Genetics; Gut microbiome; Pharmaco-metagenomics; Pharmacology; Precision medicine.

Fig. 1

A vision for the future: knowledge of the microbiome can lead to better predictions of drug response. a Currently, most medications are prescribed in a trial-and-error fashion. It has been estimated that only 30–65 % of patients respond to most drugs [5]. Non-responders need to undergo iterative rounds of trial-and-error treatments before physicians and patients arrive at an adequate drug regimen that treats disease. b Human genome sequencing has enabled physicians to predict responses to medication based on host genotype. However, this is routine clinical practice for only a few drugs and there is still considerable room to improve our predictions. c We envision a future where combined information from a person’s genome (or epigenome, proteome, metabolome) and microbiome will be used to predict the best treatment for patients. These predictions will enable tailored therapy that reduces the amount of time that patients suffer and likelihood of developing adverse effects from therapy