Mechanisms underlying the anti-Helicobacter pylori effects of Lactobacilli secretomes

全球65%的胃溃疡和癌症是由幽门螺杆菌引起的。抗生素治疗有严重的副作用，常常因为细菌耐药性而失败。在全球范围内，30%的加拿大人重新定居，人口老龄化允许更多的人在未来几十年内患上胃癌。大约95%的原住民是殖民地，胃溃疡和治疗失败的比率很高。乳杆菌是一种自然存在于肠道中的细菌，被认为是具有益生菌活性的良好细菌。行业合作伙伴Lallemand Health Solutions开发的乳杆菌制剂在体内改进了抗幽门螺杆菌的治疗方法，在Creuzenet实验室进行体外测试的20种乳杆菌中，大多数都释放了含有抗H.幽门效应。然而，这些效应背后的机制还不清楚。我们建议研究这些分子是如何工作的，测试它们针对幽门螺杆菌中特定感受器的假设。了解它们的作用机制将填补一个重要的知识空白，还将提供真正的科学证据来验证活性菌株，而这在益生菌领域往往是缺乏的。这将使我们的工业合作伙伴受益，他们有着以强有力的科学数据支持所有功效声明的良好传统。此外，我们的工作将有助于识别用于特定目的的最佳乳杆菌，并有助于识别有益的抗H。幽门螺杆菌分子，可以以纯化的形式使用，以增强混合制剂中的益生菌或增强当前抗生素治疗的疗效。这些都是对幽门螺杆菌感染患者和行业合作伙伴的直接好处，他们可以开拓一个潜在的重要市场。此外，了解幽门螺杆菌和乳杆菌之间发生的分子相互作用可以作为其他复杂细菌相互作用的模型系统。这可能会产生扩展到其他领域的应用，如营养、生物技术甚至生物修复。

The bacterium Helicobacter pylori causes 65% of gastric ulcers and cancers worldwide. Antibiotic treatmentshave serious side effects and often fail because of bacterial resistance. Globally 30% of Canadians arecolonized and the aging of the population allows more gastric cancers to develop over decades. About 95% ofAboriginals are colonized and suffer from high rates of gastric ulcers and treatment failure. Lactobacilli arebacteria naturally present in the gut that are known as good bacteria with probiotic activity. Lactobacilliformulations developed by industry partner Lallemand Health Solutions improve anti- H. pylori treatments invivo and most of the 20 Lactobacilli tested in vitro in the Creuzenet lab released molecules with anti-H. pylorieffects. However, the mechanisms underlying those effects are not understood.We propose to examine how these molecules work, testing the hypothesis that they target specific sensorspresent in H. pylori. Understanding their mechanism of action will fill an important knowledge gap and willalso provide validation of active strains by bona fide scientific evidence, which is often lacking in the probioticfield. This will benefit our industrial partner who has a well-established tradition of backing all efficacy claimsby strong scientific data.Also, our work will help identify the best Lactobacilli to be used for specific purposes and facilitate theidentification of the beneficial anti-H. pylori molecules, which could be used in purified form to potentiate liveprobiotics in mixed formulations or to enhance the efficacy of current antibiotic treatments. These are directbenefits to the H. pylori-infected patients and the industrial partner who can explore a potentially significantmarket.Furthermore, understanding the molecular interactions that occur between H. pylori and Lactobacilli couldserve as a model system for other complex bacterial interactions. This could yield applications extending toother fields, such as nutrition, biotechnology or even bioremediation.