Administration Time and Dietary Patterns Modified the Effect of Inulin on CUMS‐Induced Anxiety and Depression

Scope Prebiotics exert anxiolytic and antidepressant effects through the microbiota‐gut‐brain axis in animal models. However, the influence of prebiotic administration time and dietary pattern on stress‐induced anxiety and depression is unclear. In this study, whether administration time can modify the effect of inulin on mental disorders within normal and high‐fat diets are investigated. Methods and results Mice subjected to chronic unpredicted mild stress (CUMS) are administered with inulin in the morning (7:30–8:00 am) or evening (7:30–8:00 pm) for 12 weeks. Behavior, intestinal microbiome, cecal short‐chain fatty acids, neuroinflammatory responses, and neurotransmitters are measured. A high‐fat diet aggravated neuroinflammation and is more likely to induce anxiety and depression‐like behavior ( p < 0.05). Morning inulin treatment improves the exploratory behavior and sucrose preference better ( p < 0.05). Both inulin treatments decrease the neuroinflammatory response ( p < 0.05), with a more evident trend for the evening administration. Furthermore, morning administration tends to affect the brain‐derived neurotrophic factor and neurotransmitters. Conclusion Administration time and dietary patterns seem to modify the effect of inulin on anxiety and depression. These results provide a basis for assessing the interaction of administration time and dietary patterns, providing guidance for the precise regulation of dietary prebiotics in neuropsychiatric disorders.