The human pathogen Pseudomonas aeruginosa can rapidly induce fatal sepsis, even in previously healthy infants or children treated with appropriate antibiotics. To reduce antibiotic overuse, exploring novel complementary therapies, such as probiotics that reportedly protect patients against P. aeruginosa infection, would be particularly beneficial. However, the major mechanism underlying the clinical effects is not completely understood. We thus aimed to investigate how probiotics affect IL-8 and human beta-defensin 2 (hBD-2) in P. aeruginosa–infected intestinal epithelial cells (IECs). We infected SW480 IECs with wild type PAO1 P. aeruginosa following probiotic treatment with Lactobacillus rhamnosus GG or Bifidobacterium longum spp. infantis S12, and analysed the mRNA expression and secreted protein of IL-8 and hBD-2, Akt signalling and NOD1 receptor protein expression. We observed that probiotics enhanced hBD-2 expression but suppressed IL-8 responses when administered before infection. They also enhanced P. aeruginosa–induced membranous NOD1 protein expression and Akt activation. The siRNA-mediated Akt or NOD1 knockdown counteracted P. aeruginosa–induced IL-8 or hBD-2 expression, indicating regulatory effects of these probiotics. In conclusion, these data suggest that probiotics exert reciprocal regulation of inflammation and antimicrobial peptides in P. aeruginosa–infected IECs and provide supporting evidence for applying probiotics to reduce antibiotic overuse.

人类病原体铜绿假单胞菌可以迅速诱发致命的败血症，即使在使用适当抗生素治疗的先前健康的婴儿或儿童中也是如此。为了减少抗生素的过度使用，探索新的补充疗法，例如据报道可以保护患者免受铜绿假单胞菌感染的益生菌，将特别有益。然而，临床作用的主要机制尚不完全清楚。因此，我们旨在研究益生菌如何影响铜绿假单胞菌感染的肠上皮细胞 (IEC) 中的IL-8 和人β-防御素 2 (hBD-2 )。我们用鼠李糖乳杆菌GG 或益生菌处理后用野生型 PAO1铜绿假单胞菌感染 SW480 IECs长双歧杆菌属 infantis S12，并分析了IL-8和hBD-2的mRNA表达和分泌蛋白、Akt信号传导和NOD1受体蛋白表达。我们观察到益生菌在感染前给药时增强了 hBD-2 表达但抑制了 IL-8 反应。它们还增强了铜绿假单胞菌诱导的膜 NOD1 蛋白表达和 Akt 激活。siRNA 介导的 Akt 或 NOD1 敲低抵消了铜绿假单胞菌诱导的 IL-8 或 hBD-2 表达，表明这些益生菌的调节作用。总之，这些数据表明益生菌对铜绿假单胞菌的炎症和抗菌肽发挥相互调节作用– 受感染的 IEC，并为应用益生菌减少抗生素过度使用提供支持证据。