THE SELECTIVE SEROTONIN REUPTAKE INHIBITOR SERTRALINE AGGRAVATES EXPERIMENTAL COLITIS AND ALTERS GUT-BRAIN SIGNALING

Anxiety and depression are common comorbidities in inflammatory bowel disease (IBD) and are frequently treated with antidepressants, yet the effects of these medications on intestinal inflammation remain poorly understood. This study aimed to investigate the impact of the selective serotonin reuptake inhibitor sertraline on colitis severity, associated behavioral disturbances, inflammatory, and neurotrophic signaling in a murine model of dextran sulfate sodium (DSS)-induced colitis.
Mild colitis was induced in male C57BL/6N mice by DSS administration, followed by sertraline treatment. Disease severity was assessed using the Disease Activity Index. Anxiety- and depression-like behaviors were evaluated using a behavioral battery including the open field, elevated plus maze (EPM), and the forced swim test (FST). Expression of inflammatory, neurotrophic, and synaptic plasticity markers in the distal colon and brain was assessed by RT-qPCR and Western blotting, while serum corticosterone levels were measured by ELISA.
DSS exposure induced mild colitis accompanied by behavioral disturbances. Sertraline treatment significantly exacerbated colitis severity, increased pro-inflammatory cytokine expression in both colon and brain, and elevated serum corticosterone levels. Despite aggravated intestinal inflammation and enhanced neuroinflammation, sertraline reduced anxiety-like behavior in the EPM and tendentially improved depression-like behavior in the FST. These effects were associated with attenuation of the colitis-induced reduction in prefrontal brain-derived neurotrophic factor expression.
Overall, this work demonstrates that sertraline protects against inflammation-induced behavioral disturbances, despite aggravating colitis and neuroinflammation. Our results further indicate that sertraline might not be the antidepressant of choice for IBD patients, especially when administered during phases of active disease.