zz-1 exerts preventive effects on chronic unpredictable mild stress-induced depression in mice regulating the intestinal microenvironment.

Depression remains one of the most prevalent psychiatric disorders, and it has been confirmed that it is related to the dysfunction of the microbiota-gut-brain axis. Manipulation of the gut microenvironment by probiotics might improve mental health and prevent stress-related psychiatric disorders. The present study aimed to determine whether () zz-1 could prevent the occurrence of depression and its potential mechanisms using a mouse model with chronic unpredictable mild stress (CUMS). The results indicated that zz-1 intervention ameliorated CUMS-induced depression-like behaviors of mice with reduced body growth rate, lowered sucrose preference, increased immobility time, as well as decreased curiosity and mobility. Moreover, zz-1 significantly inhibited hormones released due to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, alleviated CUMS-induced deficits of monoamine neurotransmitters, and increased the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). These benefits were partially linked to the regulation of the intestinal microenvironment. zz-1 alleviated intestinal damage and reduced intestinal inflammation of the depressed mice. Meanwhile, zz-1 effectively adjusted the dysbiosis of mouse gut microbiota induced by CUMS, such as changes in the abundance of the NK4A136 group, , and . Taken together, these results demonstrated that zz-1 was effective in preventing depression from chronic stress, adding new evidence to support the mental benefits of probiotics.