Chronic exposure to milk odorant might ameliorate the depressive-like behavior of mice through gut-brain axis.

Mental disorders are one of the leading causes of global health burden, while food flavors play a significant role in promoting the appetite and mood of people. This study aimed to investigate the intervention effects of two kinds of pleasant food odorants on depressed mice induced by reserpine. After 6-week exposure, beef odorant and milk odorant could effectively reduced pro-inflammatory cytokines (IL-6, TNF-α), restored hippocampal structure, elevated neurotransmitters (5-HT, DA, NE), and upregulated BDNF/GFAP expression. 16S rRNA sequencing analysis revealed that both odorants could ameliorate the gut microbiota dysbiosis, increasing the relative abundance of Bacteroidetes and reducing Firmicutes. Overall, milk and beef odorants showed reletively positive effect on depressed mice through gut-brain axis, where milk odorant was more pronounced. GC-MS analysis identified oleic acid in milk odorant as a potential active component. These findings highlighted food-derived odors as promising nutritional interventions for depression through neuroinflammation modulation and microbiota-gut-brain axis regulation.