Figure 2.

Discrimination stress increases gut dysbiosis and gut permeability as well as pro-inflammatory cytokines, which reciprocally induce each other. The pro-inflammatory cytokine induction of IDO/TDO decreases tryptophan/serotonin/melatonin levels, and consequently increases kynurenine. This has mitochondrial, AhR and patterned immune/glia activity consequences. Gut dysbiosis/permeability will also impact on mitochondrial function and patterned immune/glia responses, as well as on wider epigenetic regulation, coupled to a decrease in μ-opioid receptor. This has consequences for the health disparities evident across a range of medical conditions, including MDD. Abbreviations: AhR: aryl hydrocarbon receptor; IDO: indoleamine 2,3-dioxygenase; TDO: tryptophan 2,3-dioxygenase.