Next-Generation Probiotic Therapy to Protect the Intestines From Injury.
Next-Generation Probiotic Therapy to Protect the Intestines From Injury.
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DOI：
10.3389/fcimb.2022.863949
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发表时间：
2022
影响因子：
5.7
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中科院分区：
文献类型：
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益生菌是活的微生物，当以足够的量施用时，为宿主提供健康益处。益生菌罗伊氏乳杆菌（Lactobacillus reuteri，L. reuteri）具有抗微生物和抗炎特性，可用于治疗和预防不同的胃肠道疾病，包括坏死性小肠结肠炎（NEC）和艰难梭菌（C. difficile）感染。我们的实验室开发了一种新的L. reuteri，其中益生菌与生物相容的、半渗透的、多孔的右旋糖酐微球（DM）一起孵育，所述微球可以装载有益的和可扩散的货物。L.通过在这些微球的表面上温育细菌，可以诱导罗伊氏菌形成生物膜，这增强了益生菌的功效。用蔗糖或麦芽糖负载DM诱导L。reuteri产生更多的生物膜，进一步增加益生菌的功效。采用NEC大鼠模型，L.以其生物膜状态施用的罗伊氏杆菌显著增加动物存活率、降低NEC的发生率、保持肠屏障功能并减少肠道炎症。在艰难梭菌感染的小鼠模型中，L.当在C. difficile诱导，证明了预防和治疗功效。目前没有FDA批准的用于人类的益生菌制剂。FDA批准的L.在健康成人中的生物膜状态的reuteri目前正在进行中。这项试验的结果将用于支持新生儿的I期临床试验，目的是利用L。reuteri在其生物膜状态，以防止NEC在早产儿在未来。
Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. Some strains of the probiotic Lactobacillus reuteri (L. reuteri) have both antimicrobial and anti-inflammatory properties that may be exploited for the treatment and prevention of different gastrointestinal diseases, including necrotizing enterocolitis (NEC) and Clostridioides difficile (C. difficile) infection. Our laboratory has developed a new delivery system for L. reuteri in which the probiotic is incubated with biocompatible, semipermeable, porous dextranomer microspheres (DM) that can be loaded with beneficial and diffusible cargo. L. reuteri can be induced to form a biofilm by incubating the bacteria on the surface of these microspheres, which enhances the efficacy of the probiotic. Loading the DM with sucrose or maltose induces L. reuteri to produce more biofilm, further increasing the efficacy of the probiotic. Using a rat model of NEC, L. reuteri administered in its biofilm state significantly increases animal survival, reduces the incidence of NEC, preserves gut barrier function, and decreases intestinal inflammation. In a murine model of Clostridiodes difficile infection, L. reuteri administered in its biofilm state decreases colitis when administered either before or after C. difficile induction, demonstrating both prophylactic and therapeutic efficacy. There are currently no FDA-approved probiotic preparations for human use. An FDA-approved phase I clinical trial of L. reuteri in its biofilm state in healthy adults is currently underway. The results of this trial will be used to support a phase 1 clinical trial in neonates, with the goal of utilizing L. reuteri in its biofilm state to prevent NEC in premature neonates in the future.