Abstract:This paper achieved the fixed point release of capric acid in the colon using resistant starch-capric acid（RS-CA），to study the improvement effect of capric acid on lipopolysaccharide（LPS）-induced depression in mice. Forty male ICR mice were randomly divided into five groups（blank group，LPS group，LPS+RS group，LPS+fluoxetine group，and LPS+RS -CA group）. All the intervention samples were dissolved in the drinking water of mice with volume ratio of 2∶1. Behavioral test was performed after the last intraperitoneal injection of LPS. Then the mice were sacrificed，and the eyeball blood was collected to retain the hippocampus for biochemical index detection. The colon and brain tissues were retained for HE staining. Feces were collected for 16S rRNA detection. The results showed that the mice pretreated with RS-CA performed well in the tail suspension test and open field test，and had reduced serum tumor necrosis factor- α（TNF-α）and increased hippocampus 5-hydroxytryptamine（5-HT），this indicates that RS-CA could improve the disordered arrangement of colon adenocarcinoma cells as well as the nucleus concentration and acidophilic degeneration of hippocampal neurons caused by LPS. The 16S rRNA detection revealed that RS-CA pretreatment reversed the imbalance of bacteria associated with depression；for example，Firmicutes/Bacteroidetes decreased and Prevotella，Parabacteroides，Klebsiella and Acfinobacteria returned to normal level. Additionally，the homogeneity of intestinal microbiota was improved，and thus mice in LPS+RS-CA group had the same intestinal microflora with those in blank group. The above results indicated that RS-CA could achieve antidepressant effect by regulating intestinal microbiota and reducing the inflammatory response of the hypothalamic-pituitary-adrenal axis（HPA）.