Bifidobacterium stercoris KC84 attenuates IBS-D-like symptoms via modulation of serotonin-related pathways and dendritic cell-mediated IFN-β induction

Irritable bowel syndrome with diarrhea (IBS-D) is a prevalent disorder that significantly impairs quality of life, yet therapeutic advances remain limited. Serotonin dysregulation, primarily driven by enterochromaffin cells in the intestinal epithelium, is central to IBS-D pathogenesis. We hypothesized that targeted modulation of enterochromaffin cell activity through microbiome-based interventions could provide a novel treatment approach. Here, we screened 128 Bifidobacterium isolates and identified B. stercoris KC84 as a promising candidate. KC84 alleviated IBS-D symptoms in both chemically and stress-induced models, accompanied by reduced serotonin levels. Transcriptomic analysis revealed activation of type I interferon (IFN)-associated pathways, corroborated by ex vivo evidence of KC84-induced IFN-β secretion, predominantly from type 1 conventional dendritic cells. Furthermore, IFN-β treatment attenuated contractile activity in colonic smooth muscle cells. Collectively, these findings demonstrate that KC84 mitigates IBS-D symptoms through serotonin suppression and activation of a KC84-IFN-β-smooth muscle regulatory axis, establishing KC84 as a mechanism-guided probiotic candidate for IBS-D therapy.