Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model.

The regulatory (neuro)peptide galanin and its three receptors (GALR) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GALR and GALR contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn's disease and ulcerative colitis) expressed GALR and GALR but not GALR. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GALR (GALR-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GALR resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GALR-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GALR deletion did not influence the course of colitis. In conclusion, granulocyte GALR and GALR expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GALR loss. Consequently, GALR poses a novel therapeutic target for IBD.