Abstract: The aim of the study is to investigate the protective effect of carboxymethyl pachymaran on depressive behaviour induced by sub-chronic stress. With the daily exposure to unpredictable mild stress for 2 consecutive weeks, carboxymethyl pachymaran was gavaged in mice at a daily dose of 0.1 g/kg, 0.2 g/kg or 0.4 g/kg for the last 7 days of the modelling procedure. After the experiment, the composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing, and the levels of inflammatory factors in serum were determined by ELISA, the content of short-chain fatty acids in feces was measured by GC-MS, and the depressive behaviour was evaluated by open field test and elevated plus maze test and forced swim test. Compared with the model group, low and middle doses of carboxymethyl pachymaran groups improved depression-like behaviour, and changed the composition of gut microbiota with a decrease in the relative abundance of Gram-negative bacteria (P＜0.05). In addition, the middle dose of carboxymethyl pachymaran could lower IL-2 (P＜0.05) and IL-6 (P＜0.01) levels in serum, and each dose of carboxymethyl pachymaran could down-regulate the levels of isovaleric acid and NE, 5-HT and Ach through modulating Lactobacillus and Parabacteroides relative abundance, thereby reducing the release of IL-6. In conclusion, carboxymethyl pachymaran regulated gut microbiota composition, decreased the release of gut-derived isovaleric acid and NE, 5-HT and Ach, and inhibited depression-associated inflammatory factors IL-6 and IL-2, thereby preventing depression development.

Key words: carboxymethyl pachymaran, gut microbiota, inflammation, depressive behaviour, sub-chronic stress