Biological Signature and Safety of an Immunomodulatory Probiotic Intervention for Veterans with Co-Occuring Mild TBI and PTSD

 描述（由申请人提供）： 来自最近冲突的美国退伍军人正在应对与轻度创伤性脑损伤（mTBI），持续性脑震荡（PPC）症状和创伤后应激障碍（PTSD）相关的症状。许多退伍军人对传统的健康和心理健康干预措施（例如，药物治疗、心理治疗），并且通常症状不能通过传统治疗得到显著改善。此外，对于与这两种疾病相关的症状的治疗有限，这两种疾病经常同时发生。需要替代治疗方法。mTBI和PTSD两者的一个潜在的共同潜在特征是外周和中枢神经系统中的过度炎症，其被认为在这些经常共同发生的病症的不利后果的易受伤害性、加重和永久化中起重要作用。因此，一种新的干预策略将是使用免疫调节/抗炎益生菌来减少炎症。在这项研究中，我们将研究免疫调节益生菌对全身炎症过程的生物特征和益生菌给药的近端特征的影响。罗伊氏乳杆菌（Lactobacillus reuteri）。reuteri），其是一种寄生在人肠粘膜上的微生物，通过抑制促炎细胞因子的产生来抑制粘膜炎症，并且是感兴趣的益生菌。本研究的具体目的是确定：1）L。 罗伊氏菌对肠道微生物群、肠道渗透性、全身炎症过程和应激反应的生物学特征的影响; 2）L. reuteri补充; 3）L. reuteri补充;和4）L. reuteri补充剂。将采用纵向、双盲、随机安慰剂对照设计评估项目目标。参与者将是具有PPC症状、PTSD和全身炎症升高证据（基于高基线血浆C反应蛋白[CRP]浓度）的退伍军人。在初步评估程序后，20名参与者将随机接受益生菌补充剂，20名将随机接受安慰剂补充剂。拟议的研究路线解决了康复研究与发展办公室（RR&D）服务的目标，即确定干预手段，以增加mTBI和并发精神疾病患者的功能。从长远来看，这项研究可能会导致一个范式转变的方式，我们的目标与PPC和PTSD症状相关的临床症状，通过开始支持多靶点，神经保护方法的过程。

 DESCRIPTION (provided by applicant): United States military Veterans from recent conflicts are coping with symptoms related to mild traumatic brain injury (mTBI), persistent post concussive (PPC) symptoms, and posttraumatic stress disorder (PTSD). Many Veterans are resistant to conventional health and mental health interventions (e.g., medication, psychotherapy), and often symptoms are not significantly improved by traditional treatments. Moreover, there are limited treatments for symptoms associated with both conditions, which frequently co-occur. Alternative treatment methods are needed. One potential common underlying feature of both mTBI and PTSD is exaggerated inflammation, both peripherally and in the central nervous system, which is thought to play an important role in the vulnerability to, aggravation of, and perpetuation of adverse consequences of these often co-occurring conditions. Therefore, a novel intervention strategy would be the use of immunoregulatory/anti- inflammatory probiotics to reduce inflammation. In this study, we will investigate the effects of an immunoregulatory probiotic on both biological signatures of systemic inflammatory processes and proximal signatures of probiotic administration. Lactobacillus reuteri (L. reuteri), a commensal organism that colonizes the human gut mucosa, suppresses mucosal inflammation via inhibition of the production of proinflammatory cytokines, and is the probiotic of interest. Specific aims of the study are to determine the: 1) effects of L. reuteri on biological signatures of gut microbiota, gut permeability, systemic inflammation processes, and stress responses; 2) feasibility of L. reuteri supplementation; 3) acceptability of L. reuteri supplementation; and 4) tolerability and safety of L. reuteri supplementation. Project aims will be assessed using a longitudinal, double blind, randomized placebo-controlled design. Participants will be Veterans with PPC symptoms, PTSD, and evidence of elevated systemic inflammation (based on high baseline plasma C-reactive protein [CRP] concentrations). After initial evaluation procedures, 20 participants will be randomized to probiotic supplementation and 20 will be randomized to placebo supplementation. The proposed line of research addresses the Office of Rehabilitation Research and Development (RR&D) Service's goal of identifying means of intervening to increase function among those with mTBI and co-occurring psychiatric conditions. Long-term, this study may lead to a paradigm shift in the manner by which we target clinical symptoms associated with PPC and PTSD symptoms, by beginning the process of supporting a multitargeted, neuroprotective approach.