Controlled release of coated antioxidants inhibits Citrobacter rodentium colonization in the colon of rats by reducing gut redox potential

Intestinal redox potential serves as a critical parameter reflecting the dynamic characteristics of the gut microenvironment. To precisely modulate the intestinal redox potential and evaluate its inhibition of pathogenic colonization, this study built a controlled release system and further investigated its role in gut health under a lower redox potential. The results demonstrated that the controlled release formulation significantly reduced fecal redox potential more effectively than uncoated antioxidants. By optimizing the hydrodynamic size and zeta potential of ethoxyquin (EQ) and ferulic acid (FA), the coated FA formulation maintained high efficiency in reducing redox potential and reversed body weight loss induced by pathogenic infection. Both coated EQ (EQC) and FA (FAC) selectively enriched beneficial genera, such as Lactobacillus and Limosilactobacillus, while suppressing opportunistic pathogens like Klebsiella. Notably, coated FA demonstrated enhanced efficacy in alleviating Citrobacter rodentium (C. rodentium)-induced weight loss and reducing pathogens burden compared to uncoated FA. Mechanistically, coated FA promoted the enrichment of Lactobacillus reuteri (L. reuteri), suppressed the proliferation of Enterobacteriaceae, and enhanced intestinal Muc2 gene expression. Functional metagenomic analysis revealed that FAC significantly downregulated ABC transporter activity in Enterobacteriaceae, thereby impairing biofilm formation and synergizing with mucus secretion to inhibit pathogen colonization. Further in vitro co-culture trials confirmed that under a lower redox system, L. reuteri had a stronger inhibitory effect on C. rodentium as well as the expression of their virulence genes ((tir, ler). Collectively, these findings suggest that precise modulation of colonic redox potential through controlled release strategies represents a promising approach to enhance host defense against enteric pathogens via microbiota reprogramming.