Regulation of CYP450 and drug transporter mediated by gut microbiota under high-altitude hypoxia

Xue Bai; Jianxin Yang; Guiqin Liu; Junbo Zhu; Qian Wang; Wenqi Gu; Linli La; Xiangyang Li

doi:10.3389/fphar.2022.977370

Regulation of CYP450 and drug transporter mediated by gut microbiota under high-altitude hypoxia

Front Pharmacol. 2022 Sep 15:13:977370. doi: 10.3389/fphar.2022.977370. eCollection 2022.

Authors

Xue Bai^{1

2}, Jianxin Yang¹, Guiqin Liu¹, Junbo Zhu¹, Qian Wang³, Wenqi Gu³, Linli La³, Xiangyang Li^{1

2}

Affiliations

¹ Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China.
² State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China.
³ Medical College, Qinghai University Medical College, Xining, China.

Abstract

Hypoxia, an essential feature of high-altitude environments, has a significant effect on drug metabolism. The hypoxia-gut microbiota-CYP450/drug transporter axis is emerging as a vital factor in drug metabolism. However, the mechanisms through which the gut microbiota mediates the regulation of CYP450/drug transporters under high-altitude hypoxia have not been well defined. In this study, we investigated the mechanisms underlying gut microbial changes in response to hypoxia. We compared 16S ribosomal RNA gene sequences of the gut microbiota from plain and hypoxic rats. As a result, we observed an altered gut microbial diversity and composition in rats under hypoxia. Our findings show that dysregulated gut microbiota changes CYP3A1 and MDR1 expressions in high-altitude hypoxic environments. Thus, our study reveals a novel mechanism underlying the functioning of the hypoxia-gut microbiota-CYP450/drug transporter axis.

Keywords: cytochrome P450; drug metabolism; drug transporter; gut microbiota; high-altitude hypoxia.