Human Gut Microbiota and Drug Metabolism

Abstract

The efficacy of drugs widely varies in individuals, and the gut microbiota plays an important role in this variability. The commensal microbiota living in the human gut encodes several enzymes that chemically modify systemic and orally administered drugs, and such modifications can lead to activation, inactivation, toxification, altered stability, poor bioavailability, and rapid excretion. Our knowledge of the role of the human gut microbiome in therapeutic outcomes continues to evolve. Recent studies suggest the existence of complex interactions between microbial functions and therapeutic drugs across the human body. Therapeutic drugs or xenobiotics can influence the composition of the gut microbiome and the microbial encoded functions. Both these deviations can alter the chemical transformations of the drugs and hence treatment outcomes. In this review, we provide an overview of (i) the genetic ecology of microbially encoded functions linked with xenobiotic degradation; (ii) the effect of drugs on the composition and function of the gut microbiome; and (iii) the importance of the gut microbiota in drug metabolism.

Keywords: Biotransformation; Drug metabolism; Genetic ecology; Gut microbiome; Xenobiotics.

Fig. 1

Metabolism of orally administered drugs in the human gastrointestinal tract (GI) and other body sites. Microbial loads and drug modification functions are distinct in the different parts of gastrointestinal tract. Different parts of the GI tract have different microbial load and distinct chemical environments. The parent or modified drugs may reach to the liver through portal vein or directly excrete with feces depending on the absorption attribute of the compounds. Drug excretions also take place through urinary tract

Fig. 2

Representation of bidirectional effect of gut microbiota and drugs. In a healthy individual, the gut microbiota (GM)-encoded enzymes synthesize and modify metabolites, which help in maintaining good health. However, during therapeutic interventions, there is an alteration of compositions and/or functions of GM, which act on drugs differentially, thereby resulting into altered bioavailability, reduced efficacy, and increased toxicity of drugs