Pharmacomicrobiomics: The Holy Grail to Variability in Drug Response?

Abstract

The human body, with 3.0 × 1013 cells and more than 3.8 × 1013 microorganisms, has nearly a one‐to‐one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents, i.e., pharmacomicrobiomics, has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics, and chemotherapeutic agents to human disease and treatment outcomes. We also discuss the significance of studying diet–gene–drug interactions and further address the key challenges associated with pharmacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other ‐omics data, and provide approaches to elucidate microbiome–drug interactions to improve future translation to personalized medicine.

Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study

“…MS 1 features detected in urine were normalized by the peak area of creatinine to compensate for variable concentration in random urine collection. MS 1 features detected in fecal samples were normalized by the peak area of stercobilin, a heme catabolite responsible for the brown color of feces, to compensate for variable amounts in material extracted. Blood samples were analyzed without normalization as a fixed amount of volume was extracted in each sample.…”

The Microbiome and the Gut‐Liver‐Brain Axis for Central Nervous System Clinical Pharmacology: Challenges in Specifying and Integrating In Vitro and In Silico Models

“…62,98 Host genetics play a role in gut microbiota composition, active microbial enzymes, and effects of dietary intake. 66 Today, pharmacomicrobiomics is currently limited by inadequately validated causal relationships between gut microbiota and host and the difficulty of culturing different bacterial species in the laboratory. 66 Figure 3 illustrates the variability of patient response due to differences in host metabolic phenotype and microbiota composition.…”

Pharmacogenetics: Chasing Perfection

“…As we gain deeper insights into the role of the billions of microorganisms living in the human gut, their contribution to variability in drug metabolism is also emerging. The review article by Sharma et al 30 summarizes current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents and stresses the significance of diet-gene-drug interactions. Furthermore, the authors elaborate on major challenges associated with pharmacomicrobiomics and present system biology models to tackle the integration of massive amounts of omics data.…”

“…As we gain deeper insights into the role of the billions of microorganisms living in the human gut, their contribution to variability in drug metabolism is also emerging. The review article by Sharma et al . summarizes current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents and stresses the significance of diet–gene–drug interactions.…”