2.2.4. Gut microbiota
The gut microbiota plays a central role in drug metabolism and
personalized medicine, and high-altitude hypoxia damages the gut
structure and mucosal barrier, altering the species and abundance of the
gut microbiota (Zhang et al., 2018). Gut microbiota may regulate CYP
expression (Toda et al., 2009; Togao et al., 2021; Selwyn et al., 2016).
Our group performed a study on gut microbiota and CYP expression under
high-altitude hypoxia and found that the decrease in protein and mRNA
expression of CYP3A1 under high-altitude hypoxia was substantially
correlated with changes in the structural composition and diversity of
the gut microbiota, which was mainly attributed to the upregulation of
CYP3A4 protein and mRNA expression mediated by the gut microbiota
through the release of extracellular vesicles (Bai et al., 2022), and
the study demonstrated the effects of high-altitude hypoxia on the gut
microbiota as a potential mechanism for changes in CYP expression.
As research on CYPs has advanced, it has become evident that these
mechanisms do not function autonomously. For example, the presence of
nuclear receptors is affected by epigenetic modifications, inflammatory
factors, and HIF, all of which are controlled by epigenetic
modifications. miRNAs modulate the activity of epigenetic enzymes, as
well as the expression of CYPs and nuclear receptors. Conversely, DNA
methylation and histone modification influence miRNA expression. In
summary, these mechanisms, in conjunction with hypoxia, create an
intricate network of CYP gene regulation (Figure 1).