Gut Microbiota as the Potential Mechanism to Mediate Drug Metabolism Under High-altitude Hypoxia

Abstract

Background: The characteristics of pharmacokinetics and the activity and expression of drugmetabolizing enzymes and transporters significantly change under a high-altitude hypoxic environment. Gut microbiota is an important factor affecting the metabolism of drugs through direct or indirect effects, changing the bioavailability, biological activity, or toxicity of drugs and further affecting the efficacy and safety of drugs in vivo. A high-altitude hypoxic environment significantly changes the structure and diversity of gut microbiota, which may play a key role in drug metabolism under a high-altitude hypoxic environment.

Methods: An investigation was carried out by reviewing published studies to determine the role of gut microbiota in the regulation of drug-metabolizing enzymes and transporters. Data and information on expression change in gut microbiota, drug-metabolizing enzymes, and transporters under a high-altitude hypoxic environment were explored and proposed.

Results: High-altitude hypoxia is an important environmental factor that can adjust the structure of the gut microbiota and change the diversity of intestinal microbes. It was speculated that the gut microbiota could regulate drugmetabolizing enzymes through two potential mechanisms, the first being through direct regulation of the metabolism of drugs in vivo and the second being indirect, i.e., through the regulation of drug-metabolizing enzymes and transporters, thereby affecting the activity of drugs.

Conclusion: This article reviews the effects of high-altitude hypoxia on the gut microbiota and the effects of these changes on drug metabolism.

Keywords: High-altitude hypoxia; cytochrome P450; drug metabolism; drug transporters; gut microbiota; mechanism.