Prebiotic Treatment in People with Schizophrenia

精神分裂症患者的益生元治疗

• 批准号: 10448075
• 负责人: ROBERT W BUCHANAN
• 金额: $ 16.75万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10448075
• 关键词: Acetates; Administrative Supplement; Affect; Bacteria; Behavior; Biological; Brain; Butyrates; Consent; Data; Development; Dietary Fiber; Disease; Double-Blind Method; Ensure; Funding; Grant; Growth; Immune system; Impaired cognition; Impairment; Inflammatory; Intervention; Inulin; Lead; Light; Measures; Metabolic; Multiple Abnormalities; Participant; Patient Recruitments; Personal Satisfaction; Pharmacology; Placebos; Preparation; Production; Propionates; Randomized; Randomized Clinical Trials; Schizophrenia; Serum; Specific qualifier value; Symptoms; Therapeutic; U-Series Cooperative Agreements; United States National Institutes of Health; Volatile Fatty Acids; cognitive function; design; effective therapy; functional outcomes; gut bacteria; gut microbiota; immune system function; immunoregulation; microorganism; novel strategies; prebiotics; recruit

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.

项目摘要 精神分裂症患者具有广泛的认知障碍，这是 在这种疾病的人中观察到的功能结果不佳。不幸的是，药理学和非 - 药理学干预对这些障碍的好处有限。在没有有效的情况下 疗法，认知障碍仍然是至关重要的未满足的治疗需求，而新颖的发展 他们的治疗方法仍然是一个核心的治疗挑战。在过去的10年中，大量 有证据表明，肠道菌群对脑发育有重大影响和 行为部分通过免疫系统功能的调节。肠道微生物群会影响免疫系统 通过生产短链脂肪酸（SCFA）和其他机制来功能。有三个 主要的SCFA：丁酸酯，丙酸和醋酸酯，其中丁酸酯似乎具有最明显的 对免疫系统的影响。益生元是饮食纤维，可促进肠道的生长或活性 微生物，导致宿主的福祉增强；它们已被证明增加了活动 多种不同细菌的物种，包括产生丁酸酯的细菌。鉴于新兴的证据 这表明精神分裂症的特征是免疫系统多种异常，这导致了 促炎性状态，拟议的R61项目旨在评估益生元的假设 通过增加丁酸酯的活性，管理将导致丁酸酯的产生增加 肠道菌群中的细菌；血清丁酸水平的增加将与变化有关 认知功能，症状和代谢措施。在R61项目中，我们将进行为期10天的双重 盲人，安慰剂对照，随机临床试验（RCT）确定益生元是否：前益年素（12g/天），一种 少量果糖富含纯蛋白（OEI），改变了假设的生物学特征，即增加血清丁酸血清 水平。我们将使用侵蚀蛋白 - 挑战范式来评估OEI对血清丁酸水平的影响。我们是 请求行政补充（PA-20-272：现有NIH赠款的行政补品， 合作协议）提供资金，使我们能够完成参与者的招聘 R61项目，分析数据并准备我们为R33项目提供资金的请求。我们建议使用 补充资金以招募另外11名参与者，以确保我们将有8个 参与者，将完成这项研究。我们将使用拟议的资金期限的第7个月和第8个月进行 完成数据检查，分析和准备我们对R33资金的要求。