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. 2021 May 20;13(5):1728. doi: 10.3390/nu13051728

Figure 1.

Figure 1

Illustration of potential anti-depressive mechanisms of probiotics, fundamentally involving gut microbiota modulation. The restoration of gut dysbiosis, inflammation and gut barrier dysfunction downregulates inflammation involving the TRP/KYN pathway which is implicated in depression and breaks the vicious cycles involving inflammation, the HPA-axis and persistent stimulus in the form of chronic stress. Probiotics promote synthesis of neurotransmitters either directly or indirectly by increasing BDNF levels and/or decreasing MAO levels to mediate anti-depressive effects. Probiotics attenuate exaggerated HPA-axis implicated in depression through downregulation of cortisol, proinflammatory cytokines and restoration of neurotransmitter circuits involving GABA and DA neurotransmitters. The epigenetic mechanism mainly involves butyrate-producing probiotics which inhibit HDAC and promote histone acetylation while upregulating BDNF expression. Tryptophan (TRP); Kynurenine (KYN); Indoleamine 2,3-dioxygenase (IDO); Serotonin (5-HT); Dopamine (DA); Noradrenaline (NE); Gamma-Aminobutyric acid (GABA); Brain-derived neurotrophic factor (BDNF); monoamine oxidase (MAO); Hydrogen peroxide (H2O2); Short-chain fatty acid (SCFA); Histone deacetylase (HDAC); Interleukin-6 (IL-6); Tumor necrosis factor-α (TNF-α).