Center for Perinatal Research, Department of Pediatric Surgery, Columbus, OH, United States.
Nationwide Children's Hospital, The Ohio State University, Columbus, OH, United States.
Front Cell Infect Microbiol. 2022 Jun 28;12:863949. doi: 10.3389/fcimb.2022.863949. eCollection 2022.
Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. Some strains of the probiotic () 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 () infection. Our laboratory has developed a new delivery system for in which the probiotic is incubated with biocompatible, semipermeable, porous dextranomer microspheres (DM) that can be loaded with beneficial and diffusible cargo. 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 to produce more biofilm, further increasing the efficacy of the probiotic. Using a rat model of NEC, 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 infection, administered in its biofilm state decreases colitis when administered either before or after 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 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 in its biofilm state to prevent NEC in premature neonates in the future.
益生菌是活的微生物，当以足够的量给予时，会为宿主提供健康益处。一些益生菌菌株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）和艰难梭菌感染。我们的实验室开发了一种新的益生菌输送系统，其中益生菌与生物相容的、半渗透的、多孔的葡聚糖微球（DM）孵育，可以负载有益的和可扩散的货物。可以通过在这些微球表面孵育细菌来诱导益生菌形成生物膜，从而提高益生菌的功效。用蔗糖或麦芽糖负载 DM 会诱导益生菌产生更多的生物膜，进一步提高益生菌的功效。在 NEC 的大鼠模型中，以生物膜状态给予益生菌可显著提高动物存活率，降低 NEC 的发生率，保持肠道屏障功能，并减少肠道炎症。在艰难梭菌感染的小鼠模型中，以生物膜状态给予益生菌，无论是在诱导前还是诱导后，均可减轻结肠炎，显示出预防和治疗功效。目前尚无 FDA 批准的用于人类的益生菌制剂。一项关于益生菌以生物膜状态在健康成年人中应用的 FDA 批准的 I 期临床试验正在进行中。该试验的结果将用于支持在早产儿中进行的 I 期临床试验，目标是利用益生菌以生物膜状态预防未来早产儿的 NEC。
