Administration time modify the anxiolytic and antidepressant effects of inulin via gut-brain axis

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 effects on chronic unpredictable mild stress (CUMS)-induced anxiety and depression. However, it is still unclear if the gut-brain axis is primarily responsible for these effects. In this study, fecal microbiota transplantation (FMT) confirmed that inulin administration at different times alleviated CUMS-induced anxiety- and depression-like behaviors via the gut-brain axis. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in inhibiting the inflammatory responses than that of morning inulin intervention. Serum metabolomics analysis showed that the main differential metabolites, including fenofibric acid, 4'-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may be vital for the anxiolytic and antidepressant effects of different inulin treatment times. Our results suggested that inulin administration in the evening was more effective in alleviating the inflammatory responses and improving amino acids metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, demonstrating that a more appropriate administration time results in a better intervention effect.