Supplementation with Lactobacillus kefiranofaciens ZW3 from Tibetan Kefir improves depression-like behavior in stressed mice by modulating the gut microbiota

Increasing evidence indicates that probiotics can effectively improve depression-like behavior. However, the underlying mechanism is still unclear. In this study, the antidepressant effect of Lactobacillus kefiranofaciens CGMCC2809 (ZW3) isolated from Tibetan Kefir grains was investigated using a mouse model of chronic unpredictable mild stress (CUMS). ZW3 improved depression-like behavior and independent exploration ability in the CUMS group. Moreover, ZW3 regulated biochemical disorders in the hypothalamic–pituitary–adrenal axis, immune system and tryptophan metabolism caused by stress. Furthermore, ZW3 could modulate the composition of the gut microbiota, and alleviate constipation by improving the fecal water content in stressed mice. We found that the probiotic strain was present in the whole intestine, even 7 days after its administration was stopped. These results suggest that L. kefiranofaciens ZW3 might improve depression by regulating the gut microbiota as a probiotic food.