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

• Bifidobacterium stercoris KC84 alleviates IBS-D-like symptoms in mouse and rat models • KC84 modulates serotonin-related pathways associated with diarrhea • KC84 induces IFN-β production from colonic dendritic cells • IFN-β is associated with reduced intestinal smooth muscle contractility 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-like symptoms in both chemically and stress-induced models, accompanied by changes in serotonin-related markers. Transcriptomic analysis revealed activation of type I interferon (IFN)-associated pathways, consistent with ex vivo evidence of KC84-induced IFN-β secretion, predominantly from CD11b - dendritic cells. Furthermore, IFN-β treatment attenuated contractile activity in colonic smooth muscle cells. Collectively, these findings suggest that KC84 mitigates IBS-D-like symptoms, potentially through modulation of serotonin-related pathways and activation of a KC84-IFN-β-smooth muscle regulatory axis, supporting KC84 as a mechanism-guided probiotic candidate for IBS-D therapy.