Evening inulin treatment alleviate anxiety and depression via gut-brain axis: A crucial role for microbiota and amino acids metabolism

Abstract Background Increasing evidence has demonstrated that an imbalance in the microbiota-gut-brain axis exerts an essential effect on the pathophysiology of depressive and anxiety disorders. Our previous research revealed that the timing of inulin administration altered its influence on CUMS-induced anxiety and depression; however, it is still unclear if the gut-brain axis is primarily responsible for these effects. Results Serum metabolomics analysis showed that inulin treatment can alleviate the inflammatory response in CUMS-treated mice and that amino acid metabolic pathways were crucial for its anxiolytic and antidepressant effects. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in improving amino acid metabolism and inhibiting the inflammatory response than that of morning inulin treatment. In addition, inulin treatment in the evening significantly reduced serum glucose and insulin levels. The main differential metabolites, including fenofibric acid, 4’-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may play important roles for the anxiolytic and antidepressant ability of inulin. Fecal microbiota transplantation confirmed that inulin treatment alleviated CUMS-induced anxiety- and depression-like behaviors via gut-brain axis. Conclusions Our results suggest that inulin administration in the evening is more effective in alleviating the inflammatory response and improving amino acid metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, which indicates that a more appropriate administration time results in a better intervention effect.