Biological Signature and Safety of an Immunomodulatory Probiotic Intervention of Veterans with PTSD

患有 PTSD 退伍军人的免疫调节益生菌干预的生物学特征和安全性

• 批准号: 10339332
• 负责人: Lisa A Brenner
• 金额: $ 37.09万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10339332
• 关键词: 16S ribosomal RNA sequencing; Address; Anti-Inflammatory Agents; Biological; Biological Markers; Brain; C-reactive protein; Chronic; Clinical; Communities; Conflict (Psychology); D-Amino Acid Dehydrogenase; DNA sequencing; Data; Decision Making; Diagnosis; Disease; Double-Blind Method; Evaluation; Freedom; Frustration; Funding Opportunities; Future; Gambling; Goals; Gut Mucosa; Health; Human; Impairment; Individual; Inflammation; Inflammatory; Interferon Type II; Interleukin-1 beta; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Interleukins; Intervention; Intestinal permeability; Intestines; Iowa; Irritable Bowel Syndrome; Lactobacillus casei rhamnosus; Lead; Link; Longitudinal Studies; Measures; Mediating; Mental Health; Methods; Mucositis; Neuraxis; Oral Administration; Organism; Outcome; Participant; Performance; Peripheral; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Plasma; Play; Post-Traumatic Stress Disorders; Probiotics; Procedures; Process; Production; Property; Psychotherapy; Quantitative Reverse Transcriptase PCR; Randomized; Research; Resistance; Risk; Risk Factors; Role; Safety; Severities; Stress; Supplementation; Symptoms; TNF gene; Testing; Trier Social Stress Test; United States; United States National Institutes of Health; Veterans; active duty; adverse outcome; alternative treatment; associated symptom; base; biological adaptation to stress; chemokine; cognitive process; cohort; coping; cytokine; design; efficacy trial; emotion regulation; fatty acid-binding proteins; functional outcomes; gut microbiota; immunoregulation; improved; improved functioning; inflammatory marker; innovation; microbiota; military service; military veteran; novel; operation; persistent symptom; post-traumatic symptoms; primary outcome; probiotic supplementation; psychologic; psychosocial; reduce symptoms; response; service member; symptom treatment; systemic inflammatory response

Project Summary/Abstract United States military Veterans from recent conflicts are coping with symptoms related to 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. Alternative treatment methods are needed. An underlying feature of 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 this condition. Therefore, an innovative intervention strategy would be the use of anti-inflammatory/immunoregulatory probiotics to reduce inflammation. In this study, we will investigate the effects of an 8-week oral administration of Lactobacillus rhamnosus GG (LGG; ATCC53103), a probiotic shown to have anti-inflammatory and immunoregulatory effects on both biological signatures of systemic inflammatory processes and proximal signatures of probiotic administration. LGG is a commensal organism that colonizes the human gut mucosa and suppresses mucosal inflammation via inhibition of the production of proinflammatory cytokines. The specific aim of the study is to identify the effect of probiotics on systemic inflammation, as well as PTSD symptoms, microbiota composition, gut permeability, stress response, and decision-making. Outcomes will be assessed using a longitudinal, double blind, randomized placebo-controlled design. After initial evaluation procedures to confirm PTSD and Functional Bowel Disorder diagnoses, 59 participants will be randomized to probiotic supplementation and 59 will be randomized to placebo supplementation. The proposed line of research addresses the NIH funding opportunity purpose, “to accelerate translational and clinical Phase IIa” trials regarding “probiotic[s]” to increase “understanding regarding underlying mechanisms of their action(s), and variability in responses to these interventions”. Long-term, this study may lead to a paradigm shift in the manner by which we target clinical symptoms associated with PTSD by beginning the process of supporting a multitargeted, neuroprotective approach.

项目总结/摘要 最近冲突中的美国退伍军人正在应对与创伤后应激障碍（PTSD）有关的症状。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。需要替代治疗方法。PTSD的一个潜在特征是外周和中枢神经系统的过度炎症，这被认为在这种情况的不利后果的脆弱性、加重和持续中起重要作用。因此，一种创新的干预策略将是使用抗炎/免疫调节益生菌来减少炎症。在这项研究中，我们将研究8周口服鼠李糖乳杆菌GG（LGG; ATCC 53103）的效果，这是一种益生菌，对全身炎症过程的生物特征和益生菌给药的近端特征都具有抗炎和免疫调节作用。LGG是一种肠道生物体，其定殖于人肠道粘膜并通过抑制促炎细胞因子的产生来抑制粘膜炎症。该研究的具体目的是确定益生菌对全身炎症的影响，以及PTSD症状，微生物群组成，肠道通透性，应激反应和决策。将采用纵向、双盲、随机安慰剂对照设计评估结局。在初步评估程序以确认PTSD和功能性肠病诊断后，59名参与者将随机接受益生菌补充剂，59名将随机接受安慰剂补充剂。拟议的研究路线解决了NIH资助机会的目的，“加速关于益生菌的转化和临床IIa期”试验，以增加“对其作用的潜在机制以及对这些干预措施的反应的可变性的理解”。从长远来看，这项研究可能会导致一个范式转变的方式，我们的目标与创伤后应激障碍相关的临床症状，开始支持多靶点，神经保护方法的过程。