Abstract:
Large-scale use of antimicrobials in agriculture and medicine contributes to antibiotic residues in raw foods, the spread of antimicrobial resistance (AMR) and drug pollution, which seriously threatens human health and imposes significant economic burdens on society, suggesting the need for novel therapeutic options that prevent or control zoonoses. In this study, four probiotics were selected to assess their capability to alleviate pathogen-induced damage. Results showed that a simulated gastrointestinal juice and bile tolerated L. plantarum Lac16 with high lactic acid secretion can significantly inhibit the growth of multiple zoonotic pathogens. Lac16 also significantly inhibited the biofilm formation and mRNA expression of virulence traits (genes related to virulence, toxins, flagella biogenesis and motility, antibiotic resistance, biofilm formation and AI-2 quorum sensing) of enterohemorrhagic E. coli O157:H7 (EHEC). Furthermore, Lac16 and Lac26 significantly protected C. elegans against zoonotic pathogen-induced (EHEC, S. typhimurium, C. perfringens) deaths. Moreover, Lac16 significantly promoted epithelial repair and ameliorated lipopolysaccharide (LPS)-induced intestinal epithelial apoptosis and barrier dysfunction by activating the Wnt/β-catenin signaling pathway, and markedly reduced LPS-induced inflammatory responses by inhibiting the TLR4/MyD88 signaling pathway. The present results indicate that Lac16 attenuates enterohemorrhagic E. coli infection-induced damage by inhibiting key virulence traits of E. coli, promoting epithelial repair and improving intestinal epithelial barrier function, which may be mediated by the activated Wnt/β-catenin signaling pathway and the inhibited TLR4/MyD88 signaling pathway of the intestinal epithelium.
摘要:
在农业和医学中大规模使用抗微生物剂有助于生食品中的抗生素残留,抗菌素耐药性(AMR)和药物污染的传播,严重威胁人类健康,给社会带来巨大的经济负担,这表明需要预防或控制人畜共患病的新型治疗方案。在这项研究中,我们选择了4种益生菌来评估它们减轻病原体引起的损害的能力.结果表明,具有高乳酸分泌的模拟胃肠液和胆汁耐受性的植物乳杆菌Lac16能显著抑制多种人畜共患病原菌的生长。Lac16还显着抑制了毒力性状的生物膜形成和mRNA表达(与毒力相关的基因,毒素,鞭毛生物发生和运动性,抗生素耐药性,肠出血性大肠杆菌O157:H7(EHEC)的生物膜形成和AI-2群体感应)。此外,Lac16和Lac26显着保护秀丽隐杆线虫免受人畜共患病原体诱导(EHEC,鼠伤寒杆菌,产气荚膜菌)死亡。此外,Lac16通过激活Wnt/β-catenin信号通路,显著促进上皮修复,改善脂多糖(LPS)诱导的肠上皮凋亡和屏障功能障碍,并通过抑制TLR4/MyD88信号通路显著降低LPS诱导的炎症反应。本研究结果表明,Lac16通过抑制大肠杆菌的关键毒力性状,减轻肠出血性大肠杆菌感染引起的损伤。促进上皮修复,改善肠上皮屏障功能,这可能是通过激活肠上皮的Wnt/β-catenin信号通路和抑制肠上皮的TLR4/MyD88信号通路介导的。