Prebiotic Treatment in People with Schizophrenia

精神分裂症患者的益生元治疗

• 批准号: 10677261
• 负责人: ROBERT W BUCHANAN
• 金额: $ 38.59万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677261
• 关键词: Acetates; Address; Affect; Affective Symptoms; Aftercare; Attention; Bacteria; Behavior; Biological; Brain; Butyrates; Cholesterol; Chromatin Structure; Chromosome 6; Clinical; Data; Development; Dietary Fiber; Disease; Double-Blind Method; Enzymes; Family; Fasting; Gene Expression; Genetic Polymorphism; Glucose; Growth; HDAC4 gene; Histone Deacetylase Inhibitor; Immune system; Impaired cognition; Impairment; Incidence; Inflammatory; Intervention; Intestinal permeability; Inulin; Lead; Light; Lipids; MATRICS Consensus Cognitive Battery; Measures; Mediating; Metabolic; Microglia; Multiple Abnormalities; Neurocognitive Deficit; Nuclear; Outcome; Participant; Pathway interactions; Performance; Personal Satisfaction; Persons; Pharmacological Treatment; Pharmacology; Placebo Control; Placebos; Production; Propionates; Randomized; Randomized Clinical Trials; Schizophrenia; Secondary to; Serum; Short-Term Memory; Symptoms; Therapeutic; Triglycerides; Verbal Learning; Volatile Fatty Acids; cognitive benefits; cognitive function; cognitive performance; cytokine; design; effective intervention; effective therapy; efficacy trial; executive function; functional outcomes; gut bacteria; gut microbiome; gut microbiota; immune system function; immunoregulation; improved; interest; intestinal barrier; microorganism; novel strategies; prebiotics; processing speed; psychiatric symptom; receptor; recruit; side effect; social cognition; visual learning; visual memory

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.

项目概要 精神分裂症患者存在广泛的认知障碍，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功能结果不佳。不幸的是，药理学和非 药物干预对这些损伤的益处有限。在缺乏有效措施的情况下 治疗方面，认知障碍仍然是一个未满足的关键治疗需求，并且新型药物的开发 其治疗方法仍然是一个主要的治疗挑战。过去10年，相当大 有证据表明肠道微生物群对大脑发育和 行为部分是通过免疫系统功能的调节来实现的。肠道微生物群影响免疫系统 通过产生短链脂肪酸（SCFA）和其他机制发挥作用。有三个 主要短链脂肪酸：丁酸盐、丙酸盐和乙酸盐，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性的膳食纤维 微生物，从而增强宿主的健康；它们已被证明可以增加活性 多种不同细菌种类，包括产生丁酸盐的细菌。鉴于不断出现的证据 这表明精神分裂症的特征是免疫系统的多种异常，从而导致 促炎症状态，拟议的 R61 和 R33 项目旨在评估以下假设： 益生元给药将通过增加丁酸活性来增加丁酸的产生。 在肠道微生物群中产生细菌；血清丁酸盐水平的增加将与变化相关 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， 双盲、安慰剂对照、随机临床试验 (RCT)，以确定益生元：益生物素 （12克/天），一种富含低聚果糖的菊粉（FOS），改变了假设的生物特征，即增加 血清丁酸盐水平。我们将使用菊粉挑战范例来评估 FOS 对血清丁酸盐的影响 水平。在R33项目中，我们将进行为期12周、双盲、安慰剂对照的RCT，以确认 益生元：FOS（12g/天）改变假设的生物特征：血清丁酸盐水平的能力。我们 还将检查血清丁酸盐水平的变化与 认知功能、症状和代谢指标。我们将使用 MATRICS 共识认知 用于评估认知功能变化的电池。该研究将为临床提供重要的初步数据 益生元治疗对于改善精神分裂症患者认知功能的效用。