Gut microbiota–host interplays in tryptophan and tyrosine metabolism, which affect mood and emotional states

Gut microbiota–host interplays in tryptophan and tyrosine metabolism, which affect mood and emotional states. Based on the monoamine hypothesis of depression, disruptions in brain serotonin, dopamine, or norepinephrine pathways may induce depression. The serotonin signaling pathway starts from the raphe nucleus and spreads to the entire brain, positively influencing the nucleus accumbence responsible for reward and pleasure. The enzymes TPH1 and TPH2 are involved in serotonin synthesis, and TH is involved in dopamine synthesis. Serotonin and dopamine can further proceed to produce melatonin and noradrenaline, respectively. In brain tissue, these neurotransmitters interact with glutamate (excitatory) and GABA (inhibitory) neurotransmitters, which are also implicated in the pathogenesis of depression. The gut microbiota and its metabolites play a key role in providing substrates and influencing enzymes involved in dopamine and serotonin synthesis, consequently affecting noradrenaline (particularly in locus coeruleus, LC) and melatonin (in the pineal gland) production. Melatonin regulates circadian rhythms, which are often disrupted in depression. Additionally, gut microbiota and its metabolites, especially butyrate, help mitigate blood and brain inflammation and influence the activity of the vagus nerve, which directly communicates with the brain in the medulla oblongata. The red T-shape marks indicate inhibition

Publication

Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies (2023) Shabnam Nohesara, et al. Genes (Basel). 2023 Dec;14(12). Figure: F1. Homo sapiens

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