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

针对同时发生轻度 TBI 和 PTSD 的退伍军人的免疫调节益生菌干预措施的生物学特征和安全性

• 批准号: 9274853
• 负责人: Lisa A Brenner
• 金额: --
• 依托单位: VA EASTERN COLORADO HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274853
• 关键词: Address; Adherence; Adverse effects; Adverse event; Anti-Inflammatory Agents; Anti-inflammatory; Area; Attenuated; Biological; Biological Markers; Brain; Brain Concussion; C-reactive protein; Chronic; Clinical; Cognitive deficits; Communities; Conflict (Psychology); Double-Blind Method; Evaluation; Family; Fatigue; Freedom; Frustration; Future; Goals; Headache; Health; Healthcare Systems; Human; IL8 gene; Individual; Inflammation; Inflammation Process; Inflammatory; Injury; Interleukins; Intervention; Lactobacillus reuteri; Lead; Link; Longitudinal Studies; Maintenance; Measures; Mental Health; Methods; Military Personnel; Mucositis; Mucous Membrane; Mus; Neuraxis; Oral Administration; Organism; Outcome; Participant; Performance; Peripheral; Permeability; Personality; Pharmaceutical Preparations; Placebo Control; Placebos; Plasma; Play; Polymerase Chain Reaction; Post-Concussion Syndrome; Post-Traumatic Stress Disorders; Probiotics; Procedures; Process; Production; Psychotherapy; Randomized; Recombinant DNA; Recording of previous events; Rehabilitation Research; Reporting; Research; Resistance; Risk; Role; Safety; Services; Severities; Stress; Supplementation; Symbiosis; Symptoms; TNF gene; Traumatic Brain Injury; United States; Veterans; Work; adverse outcome; affective disturbance; alternative treatment; associated symptom; base; biological adaptation to stress; chemokine; chronic pain; cohort; coping; cytokine; design; disability; efficacy trial; functional outcomes; gut microbiota; immunoregulation; improved; inflammatory marker; interest; microbial; microbial community; microbiome; microbiota; mild traumatic brain injury; neuroinflammation; novel; operation; persistent symptom; pre-clinical; probiotic supplementation; psychologic; psychosocial; public health relevance; research and development; satisfaction; service member; social stress; symptom treatment

 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.

 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(如药物、心理治疗)具有抵抗力，而且通常情况下，传统治疗并不能显著改善症状。此外，对与这两种疾病相关的症状的治疗有限，这两种症状经常同时发生。需要其他的治疗方法。MTBI和PTSD的一个潜在的共同潜在特征是外周和中枢神经系统的过度炎症，这被认为在这些经常同时发生的疾病的易感性、加重和不良后果的永久存在中发挥了重要作用。因此，一种新的干预策略将是使用免疫调节/抗炎益生菌来减轻炎症。在这项研究中，我们将调查免疫调节性益生菌对全身炎症过程的生物学特征和益生菌给药的近端特征的影响。鲁氏乳杆菌(L.reuri)是一种寄生于人体肠道粘膜的共生生物，通过抑制促炎细胞因子的产生来抑制粘膜炎症，是一种有意义的益生菌。本研究的具体目的是确定：1)L。 这些研究包括：1)罗氏乳杆菌对肠道微生物区系的生物学特征、肠道通透性、全身炎症过程和应激反应的影响；2)罗氏乳杆菌补充的可行性；3)罗氏乳杆菌补充的可接受性；以及4)罗氏乳杆菌补充的耐受性和安全性。项目目标将使用纵向、双盲、随机、安慰剂对照设计进行评估。参与者将是有PPC症状、创伤后应激障碍和全身炎症升高(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名参与者将被随机给予益生菌补充剂，20名参与者将被随机给予安慰剂补充剂。拟议的研究路线针对康复研究和发展办公室(RR&D)服务的目标，即确定干预方法，以增强患有mTBI和共生精神疾病的人的功能。从长远来看，这项研究可能会通过开始支持多靶点、神经保护方法的过程，导致我们针对与PPC和PTSD症状相关的临床症状的方式的范式转变。