BACKGROUND: Lactobacillus SlpX protein has been identified as a surface-layer protein (SLP) with the function of mediating intestinal colonization of the strain, but the mechanism of its action on intestinal immunomodulation has not yet been elucidated. In this study, we investigated the protective function of SlpX protein on the intestinal epithelial cell barrier by constructing cellular models, molecular docking and molecular dynamics simulations. RESULT: The results showed that under the stimulation of 15 ng/mL tumor necrosis factor alpha (TNF-α), the cellular barrier of Caco-2 cells was impaired, as evidenced by a decrease in transepithelial electrical resistance (TEER), an increase in permeability, and a surge in the secretion of pro-inflammatory factor interleukin 8 (IL-8) to 197.85 pg/mL. Notably, after 100 μg/mL SlpX protein was co-incubated with Caco-2 cells for 4 h, the TEER of the damaged cells increased, the permeability improved, the secretion of IL-8 was significantly inhibited, and the apoptotic index decreased to 21.09%. Molecular docking combined with 100 ns molecular dynamics simulations revealed that the SlpX protein exhibits strong binding affinities for several intestinal epithelial cell receptors, including TLR2, TLR6, CD47, and SSTR2. Notably, among the tested candidates, TLR2 emerged as the most probable target for SlpX-mediated intestinal adhesion, as evidenced by its relatively superior binding stability and energy profile. CONCLUSION: It was shown that SlpX protein effectively protects the integrity of the intestinal epithelial cell barrier by inhibiting apoptosis, reducing the secretion level of IL-8 and permeability. This study reveals the immunoprotective function of SlpX proteins, providing new insights into their role in maintaining gut health. © 2026 Society of Chemical Industry.
Zhu et al. (2026) studied this question.