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; 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 促成的R61和R33项目旨在评估以下假设，即 益生元的给药将通过增加丁酸酯的活性而导致丁酸酯的产生增加 在肠道菌群中产生细菌；血清丁酸水平的增加将与变化有关 在认知功能，症状和代谢措施中。在R61项目中，我们将进行10天 双盲，安慰剂对照，随机临床试验（RCT），以确定益生素是否：二宾 （12G/天），富含寡蛋白的菊粉（FOS），改变了假设的生物学特征，即增加 血清丁酸水平。我们将使用无蛋白 - 挑战范式来评估FOS对血清丁酸酯的影响 水平。在R33项目中，我们将进行12周的双盲，安慰剂对照，RCT，以确认 益生元：FOS（12G/天）的能力，改变假设的生物学特征：血清丁酸水平。我们 还将检查血清丁酸水平的变化与变化有关的程度 认知功能，症状和代谢措施。我们将使用Matrics共识认知 电池以评估认知功能的变化。该研究将提供有关临床的关键初步数据 益生元治疗可改善精神分裂症患者认知功能的效用。