Study on the interventional effects of Chlamydomonas reinhardtii peptides on chronic unpredictable mild stress-induced depressive-like model mice through metabolomics and microbiota

Depression is a progressive neurodegenerative disease characterized by high prevalence, high suicide rate and high recurrence rate. In this study, the protein from Chlamydomonas reinhardtii was extracted and neutral protease hydrolysate (NPH) was obtained. Its in vitro MAO-A (Monoamine oxidase A) inhibitory activity and in vivo anti-depressive effects in chronic unpredictable mild stress (CUMS) model mice were investigated. The results demonstrated that NPH can improve depressive behaviour in CUMS model mice by elevating neurotransmitter levels and alleviating hippocampal tissue structure damage. The metabolomic analysis of brain and serum samples showed that their common metabolic pathways associated with anti-depressive effects are mainly alanine, aspartate, and glutamate metabolism, glycerophospholipid metabolism, tryptophan metabolism, and caffeine metabolism. Then, the gut microbiota analysis of feces indicated that 8 species with significant changes were associated with anti-depressive effects. Finally, 5 pairs of highly correlated metabolite-bacterium pairs were identified to modulate depressive behaviours. Taken together, the present data suggests that Chlamydomonas reinhardtii-derived hydrolysate could be used for development of functional foods with potential to improve depression.