Tunable Native Probiotic Formulations for the Treatment of NEC.

尽管经过几十年的研究，坏死性小肠结肠炎(NEC)的发病率和死亡率 保持不变。肠道微生物群的改变和肠道炎症可能是易感因素 早产到NEC。益生菌可能会保护肠道免受NEC的伤害，然而，它们必须是 大量给药，并反复给药以达到任何效果。我们开发了一部小说， 鲁氏乳杆菌(LR)在保护性生物膜中的可调递送系统 生物相容微球只需一次剂量即可提供持久的益生菌益处， 大大减少了实验中的NEC。我们的长期目标是确定新的战略来保护 来自NEC的新生儿。目前的总体目标是确定一种基于益生菌的新疗法。 保护实验中的NEC。我们的中心假设是，在一个 具有生物相容微球的生物被膜状态，该微球可以装载有益的腔内货物 显著提高其定植肠道的能力，减少肠道炎症，以及 降低NEC的发生率。其基本原理是确定最佳益生菌 给药系统将导致NEC的最大益处治疗。阐明的属性 防止NEC的LR还将提供对NEC发展的关键因素的洞察。 我们将通过追求以下具体目标来客观地检验我们的中心假设： 1)确定我们的LR配方在保护肠道免受NEC伤害方面的影响。 2)调整有益的活动(生物膜形成、抗菌和抗炎 )，以优化我们的治疗配方。 3)确定调整LR的属性是否会改变其保护 来自NEC的肠子。 预期结果包括确定最有效的LR交付系统以减少 NEC，以及抗炎和抗微生物相对重要性的测定 LR在保护NEC中的作用。其重要意义在于更好地理解了 益生菌对肠道的保护，让临床以益生菌为基础的最佳设计 NEC的治疗方法。这将在提供改进的治疗方法方面产生积极影响 对有患NEC风险的患者进行干预，除了从根本上促进我们的 了解LR发挥其有益肠道效应的机制。这 研究具有创新性，因为它涉及一种新的益生菌配方：(I)只需要 单剂对NEC的有益作用和(Ii)是益生菌机制的平台 可以通过在定义良好的微球中靶向输送益生菌底物来进行研究。

Despite decades of research, the morbidity and mortality of necrotizing enterocolitis (NEC) remain unchanged. An altered intestinal microbiome and intestinal inflammation may predispose prematures to NEC. Probiotics may protect the intestines from NEC, however, they have to be delivered in high numbers with repeated dosing for any effect. We have developed a novel, tunable delivery system in which Lactobacillus reuteri (Lr) administered in a protective biofilm on biocompatable microspheres provides persistent probiotic benefits from just a single dose, greatly reducing experimental NEC. Our long-term goal is to identify novel strategies to protect neonates from NEC. The current overall objective is to identify a novel probiotic-based therapy protective against experimental NEC. Our central hypothesis is that administering Lr in a biofilm state with biocompatible microspheres that can be loaded with beneficial luminal cargo significantly improves its ability to colonize the intestines, reduce intestinal inflammation, and decrease the incidence of NEC. The rationale is that identification of an optimal probiotic delivery system will lead to maximally beneficial treatment of NEC. Elucidating the attributes of Lr that prevent NEC will also provide insight into factors essential for NEC development. We will objectively test our central hypothesis by pursuing the following specific aims: 1) To determine the impact of our Lr formulation in protection of the intestines from NEC. 2) Tuning the beneficial activities (biofilm formation, antimicrobial and anti-inflammatory effects) of Lr to optimize our therapeutic formulation. 3) To determine whether tuning the properties of Lr alters its ability to protect the intestines from NEC. Expected outcomes include identification of the most effective Lr delivery system to reduce NEC, and determination of the relative importance of anti-inflammatory and anti-microbial effects of Lr in protection from NEC. The significance is a better understanding of the effects of probiotics on protection of intestines, allowing the best design of clinical probiotic-based therapies for NEC. This will have a positive impact in terms of providing improved therapeutic interventions for patients at risk of developing NEC, in addition to fundamentally advancing our understanding of the mechanisms by which Lr exerts its beneficial intestinal effects. This research is innovative because it involves a novel probiotic formulation that: (i) requires only a single dose for beneficial effects on NEC and (ii) is a platform by which mechanisms of probiosis can be studied through targeted delivery of prebiotic substrates in well defined microspheres.