Prebiotic Treatment in People with Schizophrenia

项目总结 精神分裂症患者有广泛的认知障碍，这些障碍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较差的功能结果。不幸的是，药理上的和非 药物干预对这些损伤的益处有限。在缺乏有效的 治疗，认知障碍仍然是一个关键的未得到满足的治疗需求，以及新的 他们的治疗方法仍然是一个核心的治疗挑战。在过去的10年里，相当大的 已有证据表明，肠道微生物区系对大脑发育和 行为在一定程度上是通过调节免疫系统的功能来实现的。肠道微生物区系影响免疫系统 通过产生短链脂肪酸(SCFA)和其他机制发挥作用。一共有三个 主要单链脂肪酸：丁酸盐、丙酸和醋酸盐，其中丁酸盐似乎最明显 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，这会增强宿主的幸福感；它们已被证明可以提高活性 多种不同的细菌种类，包括生产丁酸的细菌。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重异常，这会导致 对于促炎状态，拟议的R61和R33项目旨在评估以下假设 益生素给药将通过增加丁酸盐的活性来增加丁酸盐的产量。 在肠道微生物区系中产生细菌；血清丁酸水平的增加将与变化相关 在认知功能、症状和新陈代谢方面。在R61项目中，我们将进行为期10天的， 双盲、安慰剂对照、随机临床试验(RCT)，以确定益生元：前生物素 (12g/天)，一种富含低聚果糖的菊粉(FOS)，改变了假想的生物学特征，即增加 血清丁酸水平。我们将使用菊粉-挑战范式来评估低聚果糖对血清丁酸的影响 级别。在R33项目中，我们将进行为期12周的双盲、安慰剂对照RCT，以确认 益生素的能力：FOS(12g/天)，改变假想的生物学特征：血清丁酸水平。我们 还将检查血清丁酸水平的变化与 认知功能、症状和新陈代谢指标。我们将使用Matrics共识认知 电池来评估认知功能的变化。这项研究将为临床提供关键的初步数据 益生素治疗对改善精神分裂症患者认知功能的作用。

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 and R33 projects are 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 (FOS), alters the hypothesized biological signature, i.e., increases serum butyrate levels. We will use an inulin-challenge paradigm to asses the effect of FOS on serum butyrate levels. In the R33 project, we will conduct a 12-week, double-blind, placebo-controlled, RCT, to confirm the ability of the prebiotic: FOS (12g/day), to alter the hypothesized biological signature: serum butyrate levels. We will also examine the extent to which changes in serum butyrate levels are associated with changes in cognitive function, symptoms, and metabolic measures. We will use the MATRICS Consensus Cognitive Battery to assess change in cognitive function. The study will provide critical preliminary data on the clinical utility of prebiotic treatment for the improvement of cognitive function in people with schizophrenia.