Paroxetine alleviates ulcerative colitis in mice via restoring intestinal microbiota homeostasis and metabolism

Ulcerative colitis (UC) is an inflammatory bowel disease and psychological factors may be one of its pathogeneses. Selective serotonin reuptake inhibitor drug such as paroxetine with an effective anti-depression ability may be a new option for UC treatment. To evaluate the therapeutic effect of paroxetine on the exacerbation of UC symptoms caused by depression, a dual model of C57BL/6 mice was established using dextran sulphate sodium and chronic unpredictable mild stress (CUMS). Behavioural experiments, H&E staining and the level of 5-hydroxytryptamine (5-HT) in the brain were used to demonstrate successful replication of the CUMS model. The levels of 5-HT, TNF-α and IL-1β in the colon and the activity of MPO in the serum were determined by ELISA kits. The levels of some gut microbiota in the faeces were measured by qPCR and faecal differential metabolites were analysed by ¹H NMR. The results indicate that CUMS can exacerbate UC symptoms in mice by exacerbating inflammation, and UC+CUMS can disrupt gut microbiota and fatty acid metabolism. Paroxetine can improve the mental state of mice, reduce serum MPO activity, but increase TNF-α and IL-1β levels in the colon. In addition, paroxetine also can restore the intestinal flora of mice and improve intestinal absorption and metabolic function of amino acids and short-chain fatty acids.