Ulcerative colitis is a long-lasting, immune-driven condition of uncertain origin, occurring across various age groups and markedly impairing daily functioning. Current therapeutic strategies predominantly rely on anti-inflammatory agents and do not specifically target the underlying pathogenic mechanisms. In this work, we examined how transferring a sterile filtrate of stool from healthy individuals influences the activation of anti-inflammatory immune pathways. We found that this intervention in ulcerative colitis patients led to the emergence of T helper cells in circulation that recognized components of the sterile filtrates in an antigen-dependent fashion and secreted IL-10. In contrast, cells obtained from the same individuals prior to treatment responded weakly to these filtrates and mainly released IL-4, reflecting a more pro-inflammatory profile. These findings indicate that transplantation of a sterile stool filtrate promotes a shift toward an anti-inflammatory T-helper phenotype, an effect that strengthened and remained detectable for at least three months following the procedure.
