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

项目摘要/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(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。需要其他的治疗方法。创伤后应激障碍的一个基本特征是外周和中枢神经系统的过度炎症，这被认为在这种疾病的不利后果的易感性、加重和永久化方面发挥了重要作用。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，我们将研究口服鼠李糖乳杆菌GG(LGG；ATCC53103)8周的效果，这是一种被证明具有抗炎和免疫调节作用的益生菌，对全身炎症过程的生物学特征和益生菌给药的近端特征都有影响。LGG是一种共生生物，通过抑制促炎细胞因子的产生来定植于人的肠道粘膜并抑制粘膜炎症。这项研究的具体目的是确定益生菌对全身炎症以及创伤后应激障碍症状、微生物区系组成、肠道通透性、应激反应和决策的影响。结果将使用纵向、双盲、随机、安慰剂对照设计进行评估。在初步评估程序以确认创伤后应激障碍和功能性肠道疾病的诊断后，59名参与者将被随机分配到益生菌补充剂，59名参与者将被随机分配到安慰剂补充剂。拟议的研究方向解决了美国国立卫生研究院资助机会的目的，即“加快翻译和临床IIa期”关于“益生菌[S]”的试验，以增加“对其作用的潜在机制(S)的理解，以及对这些干预措施反应的可变性”。从长远来看，这项研究可能会导致范式的转变，我们通过开始支持多靶点、神经保护方法的过程来针对与创伤后应激障碍相关的临床症状。

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.