Immunoglobulin Y protects intestinal epithelium and modulates gut microbiota

Aim: This study investigated the effects of Muno-IgY®, a multi-pathogen-specific immunoglobulin Y (IgY), on microbial growth, adhesion, fermentation activity, and immune signaling using a multi-tiered in vitro approach. Methods: IgY activity was first evaluated in Caco-2 adhesion and invasion assays using adherent-invasive Escherichia coli (AIEC) at optimized concentrations, followed by assessment in a SHIME® in vitro gut model inoculated with human fecal microbiota enriched in Enterobacteriaceae. Microbial composition, fermentation markers, and metabolite production were analyzed, and downstream effects on epithelial barrier integrity and immune signaling were evaluated using a Caco-2/peripheral blood mononuclear cell (PBMC) co-culture model exposed to SHIME® effluents. Results: Muno-IgY® significantly reduced AIEC adhesion/invasion from 39.76% in controls to 13.08% and 9.13% at 3 and 6 mg/mL, respectively (P < 0.05). In the SHIME® model, IgY significantly increased acetate and propionate production (P < 0.05), alongside a marked increase in ammonium concentration (P < 0.01). Microbial biomass increased modestly, while alpha- and beta-diversity indices were not significantly altered. The compositional shifts indicated enrichment of beneficial and mucin-associated taxa and reduction of opportunistic or pathogenic species in the Muno-IgY® group. In Caco-2/PBMC co-cultures, IgY-treated effluent decreased transepithelial electrical resistance (TEER) indicating reduced barrier integrity (P < 0.05) but significantly decreased pro-inflammatory cytokines Interferon-γ (IFN-γ) and Interleukin-22 (IL-22) (P < 0.05). Conclusions: Muno-IgY® demonstrates the ability to inhibit pathogen adhesion and modulate microbial composition and immune responses in vitro. These findings support its potential as a non-antibiotic approach for microbiome-targeted interventions, although further validation in vivo is required.