Tryptophan-rich diet ameliorates chronic unpredictable mild stress induced depression- and anxiety-like behavior in mice: The potential involvement of gut-brain axis

Tryptophan, an essential amino acid, has been reported that it has the potential to regulate depression-like behavior. Meanwhile, Chronic stress-induced depression also has a close relationship with gut microbiota structure and composition. In the current research, we demonstrated that a tryptophan-rich diet (0.6% tryptophan w/w) significantly attenuated depression- and anxiety-like behaviors in a chronic unpredictable mild stress (CUMS)-treated mouse model. Tryptophan supplementation improved neuroinflammation, increased expression of BDNF, and improved mitochondrial energy metabolism in the brain of CUMS-treated mice. Besides, CUMS also enhanced the kynurenine pathway, but repressed the serotonin pathway and indole pathway of tryptophan metabolism, leading to a decrease in 5-HT and indole in serum, whereas tryptophan supplementation might shift the tryptophan metabolism more toward the serotonin pathway in CUMS-treated mice. The gut microbiome was restructured by increasing the relative abundance of Lachnospiracea, Clostridium, Lactobacillus, Bifidobacterium in tryptophan-treated depressive mice. Moreover, tryptophan administration inhibited stress-induced gut barrier damage and decreased inflammatory responses in the colon. Together, our study purports the gut-brain axis as a mechanism for the potential of tryptophan to improve depression and anxiety-related behavior.