Current Evidence from Animal Models on Molecular Changes Underlying Antidepressant Effects of Psychobiotics

The treatment of depression is an uphill battle due to the low efficiency and delayed clinical response of antidepressants and the fact that most of them cause numerous side effects. Psychobiotics, probiotics that affect brain function and confer mental health benefits, emerged as a promising ally showing protective effects against depressive- and anxiety-like behaviors in various animal models of depression. There is rapidly accumulating evidence that psychobiotics show protective effects at the molecular level as well, affecting several pathophysiological processes implicated in depression. This narrative review summarizes preclinical insights into molecular changes related to the hypothalamic-pituitary-adrenal (HPA) axis, peripheral inflammation, neuroinflammation, neurotransmission and tryptophan metabolism underlying psychobiotic-driven mitigation of depressive and anxiety symptoms in stress-based, corticosterone-induced and inflammation-induced animal models of depression. Research evidence indicates that psychobiotics normalize the activity of the HPA axis, decrease levels of inflammatory mediators in the intestine, circulation, and brain, normalize the levels of neurotransmitters and their receptors, and regulate tryptophan metabolism in various animal models of depression. The main setbacks in this field are the extensive diversity of studied probiotic strains, which are often insufficiently characterized, and the lack of mechanistic studies in animal models. However, despite these challenges, further study of psychobiotics in the pursuit of supportive therapies for depressive disorders is firmly grounded.