Prophylactic effects of supplementation of a combination of Lactobacillus lactis WHH2078 and saffron on depressive-like behaviors in mice exposed to chronic stress.

Depression is one of the most common psychiatric conditions worldwide, with an annual escalation in prevalence. The serotonin (5-Hydroxytryptamine [5-HT]) metabolism through the gut-brain axis has been revealed to be related to the development of depression. Our previous study demonstrated that Lactococcus lactis WHH2078 alleviated depression in mice by shaping the gut microbiome composition and 5-HT metabolism. However, little research has explored the synergistic effects of probiotics and natural mental health-improving products. In this study, three natural products (saffron, l-theanine, and phosphatidylserine), either individually or in combination, were orally administrated for 4 weeks in chronic restraint stress (CRS)-induced mice, and their depressive behaviors, hippocampal 5-HT, and serum corticosterone were assessed. Saffron demonstrated improvement of the depressive-like behaviors via multiple behavioral tests and reversed the declined concentration of 5-HT and increased concentration of corticosterone. Following an initial screening, saffron was chosen to be combined with WHH2078, referred to as WHHMOOD™. Furthermore, the effects of WHHMOOD were evaluated in mice with depressive-like behaviors. WHHMOOD reduced immobility time in the forced swimming test and tail suspension test, increased the time spent in the central area in open field test, and reduced the serum corticosterone level. Besides, WHHMOOD improved the CRS-induced gut microbial dysbiosis by reversing gut microbial diversity and the abundances of Ligilactobacillus, Candidatus Arthromitus, and Erysipelatoclostridium. Compared to WHH2078, WHHMOOD treatment significantly increased the travel distance and hippocampal 5-HT level in mice. In conclusion, WHHMOOD exhibited prophylactic effects on depressive-like in CRS mice, which may act as a promising agent for improving the symptoms of depression.