Enterococcus faecalis NBRC 100481 Protects the Intestinal Barrier via α-catenin/HMP-1 in Caenorhabditis elegans.

Intestinal barrier disruption is a hallmark of gastrointestinal disorders and is also linked to metabolic diseases, posing serious health risks. Probiotic-based interventions have thus attracted growing attention. This study isolated Enterococcus faecalis NBRC 100481 from recovered colitis mice after dietary intervention with pentagalloyl glucose (PGG), and evaluated its protective effects and PGG's regulatory role. Fermentation revealed that PGG enhanced metabolic activity of E. faecalis NBRC 100481 and promoted production of bioactive metabolites such as N-acetylglutamic acid and 4-hydroxybenzaldehyde, which reduced intestinal permeability in Caenorhabditis elegans model. The strain also modulated host responses by preserving epithelial structure and suppressing aberrant expression of VHA-6. Its protective effects were abolished in zoo-1 and hmp-1 mutant worms, suggesting a dependence on host adhesion protein-related pathways. Notably, it attenuated the injury-induced upregulation of α-catenin/HMP-1 in worms with intestinal injury. Collectively, E. faecalis NBRC 100481, modulated by PGG, enhances intestinal barrier function through coordinated microbial metabolite production and host regulatory pathways, with the α-catenin/HMP-1 axis involved as a downstream component. This study offers new insights into polyphenol-probiotic-host interactions and provides strain-level evidence for probiotic-based barrier repair strategies.