ArticleScientific reports2026
Lactobacillus yoelii Lac-2 mediates the mechanism of MAPK signaling pathway involved in the regulation of intestinal barrier and pathogen translocation by Zonulin expression.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Yak is an endemic livestock on the Qinghai-Tibet Plateau, which is prone to diarrhea caused by intestinal pathogenic bacteria. In the context of insufficient vaccines and antibiotic resistance, screening lactic acid bacterial strains adapted to high-altitude environments has become a novel approach for the prevention and treatment of diarrhea. This study explored the mechanism by which Lactobacillus yoelii Lac-2 regulates the intestinal barrier and pathogen translocation via the MAPK pathway, with a focus on zonulin expression. Zonulin up-regulation and knockdown were performed in intestinal epithelial cell lines, and a monolayer epithelial barrier was established using Transwell chambers. The cells were divided into four groups: control group, Escherichia coli (E. coli) O78 model group, low- and high-dose Lactobacillus yoelii Lac-2 groups. MAPK agonist and inhibitor were added to the corresponding groups, respectively. The expressions of zonulin, mucins (MUC1, MUC2), and tight junction proteins (ZO-1, Occludin, Claudin 1) were detected by RT-qPCR and Western blot. The barrier integrity was evaluated by transepithelial electrical resistance (TEER), FITC-dextran (FD4) permeability, and flow cytometry to detect bacterial translocation and cell apoptosis levels. The results confirmed that zonulin up-regulation and knockdown cell lines were successfully constructed, and the MAPK pathway was effectively intervened. Zonulin upregulation and MAPK pathway activation significantly decreased TEER, increased FD4 permeability and bacterial translocation, downregulated the expressions of MUC1, MUC2, ZO-1, Occludin, and Claudin 1, and promoted cell apoptosis, thereby impairing the intestinal barrier protective effect of Lactobacillus yoelii Lac-2. Collectively, yak-derived Lactobacillus yoelii Lac-2 can reduce zonulin expression by inhibiting the MAPK signaling pathway, maintain the tight junction structure, and decrease pathogenic bacterial translocation, thereby alleviating E. coli O78-induced intestinal epithelial barrier damage and exerting a protective effect on the intestinal barrier.
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