Prebiotic Treatment in People with Schizophrenia

项目摘要 精神分裂症患者有广泛的认知障碍，这是精神分裂症的主要决定因素。 在患有这种疾病的人中观察到的不良功能结果。不幸的是，药理学和非- 药物干预对这些损伤的益处有限。如果缺乏有效的 尽管目前的治疗方法中，认知障碍仍然是一个关键的未满足的治疗需求，并且新的治疗方法的开发， 其治疗方法仍然是一个中心的治疗挑战。在过去的10年里， 已有证据表明，肠道微生物群对大脑发育有显著影响， 行为，部分是通过调节免疫系统的功能。肠道微生物群影响免疫系统 通过产生短链脂肪酸（SCFAs）和其他机制发挥作用。有三 主要SCFAs：丁酸盐、丙酸盐和乙酸盐，其中丁酸盐似乎具有最明显的 对免疫系统的影响益生元是促进肠道生长或活动的膳食纤维 微生物，这导致宿主的福祉增强;它们已被证明可以增加活性 多种不同的细菌物种，包括丁酸生产细菌。根据新出现的证据 这表明精神分裂症的特征是免疫系统的多种异常， 促炎状态，拟议的R61项目旨在评估益生元 施用将通过增加丁酸盐产生酶的活性而导致丁酸盐的产生增加。 肠道菌群中的细菌;血清丁酸盐水平的增加将与 认知功能、症状和代谢指标。在R61项目中，我们将进行为期10天的双- 一项盲法、安慰剂对照、随机临床试验（RCT），以确定益生元：Prebiotin（12 g/天）， 富含低聚果糖的菊粉（OEI），改变了假设的生物特征，即，增加血清丁酸盐 程度.我们将使用菊糖激发范例来评估OEI对血清丁酸水平的影响。我们 申请行政补充（PA-20-272：现有NIH赠款的行政补充， 合作协议），以提供资金，使我们能够完成我们的参与者招募，为目前的 R61项目，分析数据并准备R33项目的资金申请。我们建议使用 补充资金，以招募额外的11名参与者，以确保我们将有8个以上 参与者将完成研究。我们将利用拟议供资期的第7和第8个月， 完成数据检查和分析，并准备我们的R33资金申请。

PROJECT SUMMARY People with schizophrenia have a broad range of cognitive impairments, which are major determinants of the poor functional outcome observed in people with this disorder. Unfortunately, pharmacological and non- pharmacological interventions have limited benefits for these impairments. In the absence of effective treatments, cognitive impairments remain a critical unmet therapeutic need, and the development of novel approaches for their treatment remains a central therapeutic challenge. Over the past 10 years, considerable evidence has emerged to suggest that the gut microbiota has significant effects on brain development and behavior, in part, through the regulation of immune system function. The gut microbiota affects immune system function through the production of short chain fatty acids (SCFAs) and other mechanisms. There are three major SCFAs: butyrate, propionate, and acetate, of which, butyrate appears to have the most pronounced effects on the immune system. Prebiotics are dietary fibers that promote the growth or activity of gut microorganisms, which leads to enhanced well-being of the host; they have been shown to increase the activity of multiple different bacteria species, including butyrate-producing bacteria. In light of the emerging evidence that suggests schizophrenia is characterized by multiple abnormalities of the immune system, which lead to a pro-inflammatory state, the proposed R61 project is designed to evaluate the hypothesis that prebiotic administration will lead to increased production of butyrate, through increased activity of butyrate-producing bacteria in the gut microbiota; the increase in serum butyrate levels will be associated with changes in cognitive function, symptoms, and metabolic measures. In the R61 project, we will conduct a 10-day, double- blind, placebo-controlled, randomized clinical trial (RCT) to determine if the prebiotic: Prebiotin (12g/day), an oligofructose-enriched inulin (OEI), alters the hypothesized biological signature, i.e., increases serum butyrate levels. We will use an inulin-challenge paradigm to assess the effect of OEI on serum butyrate levels. We are requesting an administrative supplement (PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements) to provide funds to enable us to complete our participant recruitment for the current R61 project, analyze the data and prepare our request for funding of the R33 project. We propose to use the supplemental funds to recruit an additional 11 participants, in order to ensure that we will have 8 more participants, who will complete the study. We would use months 7 and 8 of the proposed funding period to complete data checking and analyses and preparation of our request for R33 funding.