Laboratoire de Microbiologie, CH Cornouaille, Rue Yves Thepot, 29000 Quimper, France.
Univ Brest, Inserm, EFS, UMR 1078, GGB, 22 avenue Camille Desmoulins, 29200 Brest, France.
Benef Microbes. 2019 Dec 9;10(8):893-900. doi: 10.3920/BM2019.0069. Epub 2019 Oct 10.
The spreading of antibiotic resistance is a major public health issue, which requires alternative treatments to antibiotics. Lactobacilli have shown abilities to prevent pneumonia in clinical studies when given by oral route, certainly through the gut-lung axis involvement. Rationally, respiratory administration of lactobacilli has been developed and studied in murine model, to prevent from respiratory pathogens. It allows a direct effect of probiotics into the respiratory system. To our knowledge, no study has ever focused on the effect of probiotic intra-respiratory administration to prevent from (PA) pneumonia, a major respiratory pathogen associated with high morbidity rates. In this study, we evaluated the beneficial activity of three strains ( K.C6.3.1E, Od.76, ES.D.88) previously screened by ourselves and known to be particularly efficient in inhibiting PAO1 virulence factors. Cytotoxic assays in alveolar epithelial cell line A549 were performed, followed by the comparison of two lactobacilli prophylactic protocols (one or two administrations) by intra-tracheal administration in a C57BL/6 murine model of PA pneumonia. A549 cells viability was improved from 23 to 75% when lactobacilli were administered before PAO1 incubation, demonstrating a protective effect (0.001). A significant decrease of 2 log of PAO1 was observed 4 h after PAO1 instillation (3×10 cfu/mouse) in both groups receiving lactobacilli (9×10 cfu/mouse) compared to PAO1 group (<0.05). One single prophylactic administration of lactobacilli significantly decreased the secretion by 50% in bronchoalveolar lavages of interleukin (IL)-6 and tumour necrosis factor-α compared to PAO1. No difference of secretion was observed for the IL-10 secretion, whatever the prophylactic study design. This is the first study highlighting that direct lung administration of strains protect against PA pneumonia. Next step will be to decipher the mechanisms involved before developing this novel approach for human applications.
抗生素耐药性的传播是一个主要的公共卫生问题，这需要替代抗生素的治疗方法。在临床研究中，经口服途径给予乳杆菌可显示出预防肺炎的能力，这肯定是通过肠道-肺部轴的参与。从理论上讲，已经开发并研究了乳杆菌的呼吸道给药，以预防呼吸道病原体。它允许益生菌直接作用于呼吸系统。据我们所知，尚无研究关注过呼吸道内给予益生菌以预防肺炎（PA）的作用，肺炎是一种与高发病率相关的主要呼吸道病原体。在这项研究中，我们评估了三种先前由我们筛选出的菌株（K.C6.3.1E、Od.76、ES.D.88）的有益活性，这些菌株已知特别有效地抑制 PAO1 毒力因子。在肺泡上皮细胞系 A549 中进行细胞毒性测定，然后通过比较两种乳杆菌预防性方案（一次或两次给药），通过气管内给药在 PA 肺炎的 C57BL/6 小鼠模型中进行。当在 PAO1 孵育之前给予乳杆菌时，A549 细胞的活力从 23%提高到 75%，证明了保护作用（0.001）。在接受乳杆菌的两组中，在 PAO1 感染后 4 小时观察到 PAO1 的减少了 2 个对数级（3×10 cfu/小鼠），与 PAO1 组相比（<0.05）。与 PAO1 相比，乳杆菌的单次预防性给药可使支气管肺泡灌洗液中的白细胞介素（IL）-6 和肿瘤坏死因子-α的分泌减少 50%。无论预防性研究设计如何，IL-10 的分泌均无差异。这是第一项研究表明，直接肺部给予这些菌株可预防 PA 肺炎。下一步将是在开发这种新方法用于人类应用之前，阐明所涉及的机制。
