Yeast Extract Peptides Alleviate Depression in Chronic Restraint Stress Rats by Alleviating Hippocampal Neuronal Apoptosis and Dysbiosis of the Gut Microbiota

Scope Depression as a global neurological disorder, and hippocampal neuronal apoptosis and disorders of the gut microbiota are closely related to it. This study aims to expose the ameliorative effect of enzyme peptides (AP) from brewer's yeast on depressive behavior caused by chronic restraint stress (CRS) in rats. Methods and results After 4 weeks of AP intervention, a significant alleviation of depressive behavior in the sucrose preference test (SPT), forced swim test (FST), and light‐dark test (LDT) is observed in depressed rats. AP ameliorates neuronal damage with increased the expression of the key CREB/BDNF/TrkB/Akt signaling pathway, which increases the levels of the monoamine neurotransmitters 5‐hydroxytryptamine (5‐HT) and norepinephrine (NE) in the hippocampus, buffering hyperactivity of the hypothalamo‐pituitary‐adrenal axis (HPA), and decreasing the serum cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in rats. In addition, AP modulates the disruption of the rat gut microbiota by chronic restraint stress (CRS), and the changes in the abundance of Lactobacillus animalis and Lactobacillus johnsonii are probably the key for AP performing antidepressant benefits. A strong correlation is found between gut microbiota and biochemical markers of depression. Conclusion AP, as a natural and safe active substance, has a positive effect in the treatment of depression.