Abstract: A large number of studies have confirmed that the “microorganism-gut-brain axis” plays an important role in the development of depression, and the short chain fatty acids(SCFAs)produced by gut microbiota are the key molecules involved in neuromodulation. In this study, for the first time, SCFA-acylated starches were used to release 5 types of SCFAs in the large intestine, to explore their alleviation effects on chronic unpredictable mild stress (CUMS)-induced depression in mice and its mechanisms. Using male C57BL/6J mice as the research object, a five-week intervention was used to construct a depressive mice model, and the depression-like behaviors of the mice were evaluated through the open field test, elevated plus maze test and forced swimming test. At the same time, the concentration of stress hormones, neurotransmitters and the gene expression of related enzyme in mice were detected. The results showed that acetic acid, isobutyric acid and butyric acid can alleviate depression-like behaviors in mice to varying degrees. The possible mechanisms are related to SCFAs repairing the hypothalamic-pituitary-adrenal axis feedback regulation disorder and restoring normal metabolism of 5-hydroxytrptamine. This study provides a new theoretical basis for nutrition intervention of depression.
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