Spermidine ameliorates colitis via induction of anti-inflammatory macrophages and prevention of intestinal dysbiosis

Niechcial et al assessed the effect of oral spermidine administration on colitis severity, the intestinal microbiome, and intestinal barrier integrity  in the T cell transfer colitis model in Rag2 -/- mice. Their findings, as put forward in their recently published manuscript, confirm the colitis-protective and anti-inflammatory properties of spermidine and demonstrate that these effects are mediated by the anti-inflammatory molecule protein tyrosine phosphatase non-receptor type 2 (PTPN2) in intestinal epithelial cells and monocytic myeloid cells. Our data further suggest that spermidine acts in multiple ways by promoting anti-inflammatory macrophages, maintaining a healthy gut microbiome, and preserving epithelial barrier integrity. These three components heavily influence each other and collectively maintain intestinal homeostasis. By positively influencing these factors in the absence of overt negative effects, spermidine administration might represent a promising novel therapeutic strategy for the treatment of inflammatory bowel disease.