INTESTINAL PERMEABILITY IN CHILDREN WITH AUTISM SPECTRUM DISORDERS

自闭症谱系障碍儿童的肠道通透性

• 批准号: 7605111
• 负责人: ANN E REYNOLDS
• 金额: $ 3.21万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605111
• 关键词: Affect; Alternative Therapies; Autistic Disorder; Autoantibodies; Blood; Brain; Caseins; Celiac Disease; Child; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnosis; Diet; Disease; Enrollment; Family; Feces; Funding; General Population; Gluten; Grant; Individual; Institution; Intervention; Intestines; Literature; Medical; Milk; Neurodevelopmental Disorder; Opioid; Permeability; Population; Proteins; Questionnaires; Recruitment Activity; Reporting; Research; Research Personnel; Resources; Serum; Small Intestines; Source; Statistically Significant; Testing; Tight Junctions; Time; Tissues; Transglutaminases; United States National Institutes of Health; Wheat; autism spectrum disorder; base; day; gastrointestinal symptom; theories; zonulin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autism is a complex neurodevelopmental disorder. There are currently no scientifically validated medical treatments for autism, however, there are many complimentary and alternative therapies. Gastrointestinal symptoms have been reported in 15-20% of children with autism spectrum disorders and many theories about the cause of autism arise from GI related issues. The lay literature recommends using a gluten and casein free diet in children with autism based on the "opiod theory." In this theory milk (casein) and wheat (gluten) proteins are incompletely broken down in the intestine, absorbed by a "leaky gut" and exert an "opioid-like" effect in the brain. The only supporting evidence for increased intestinal permeability in children with autism was reported by D'Eufemia in a small population of children with autism(1). In a study of children with high functioning autism without gastrointestinal symptoms, D'Eufemia, et al found abnormal intestinal permeability in 9 of 21 children. Despite the lack of scientific data to support the gluten and casein free diet, many families put their children on the diet. This is probably due to the fact that there is no cure for autism. The diet is difficult to follow, expensive and time consuming. Accurate information is very important for the families of children with autism, so that they may make well informed decisions about interventions for their children. This study will be a more comprehensive assessment of intestinal permeability. Two groups of subjects with autism spectrum disorders (ASD) will be compared to control subjects. Thirty-seven subjects with ASD on a gluten and casein free diet and 37 subjects on an unrestricted diet will be enrolled. It is unlikely that diet will effect intestinal permeability but gluten does increase intestinal permeability in individuals with celiac disease, therefore both groups will be included seperatedly. A group of 37 should give adequate power to detect a statistically significant difference between groups. This study will test for serum autoantibodies found in celiac disease which is a disorder of the small intestine associated with increased intestinal permeability and sensitivity to gluten. Celiac disease can be asymptomatic and may occur in as many as 1% of the general population. Serum zonulin levels will also be evaluated as zonulin has been associated with abnormal intestinal tight junctions and may affect intestinal permeability. Subjects will have a research reliable diagnosis of autism and will complete questionnaires regarding gastrointestinal symptoms and keep a 7 day stool record. Thirty-seven control subjects with typical development will be recruited for the intestinal permeability study and questionnaires only. Control subjects will have blood drawn for tissue transglutaminase only if their intestinal permeability study is abnormal.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 自闭症是一种复杂的神经发育障碍。目前还没有经过科学验证的治疗自闭症的药物，然而，有许多免费和替代疗法。 据报道，15-20%的自闭症谱系障碍儿童有胃肠道症状，许多关于自闭症原因的理论都来自胃肠道相关问题。 非专业文献建议根据“阿片理论”对自闭症儿童使用无麸质和酪蛋白的饮食。在这个理论中，牛奶（酪蛋白）和小麦（麸质）蛋白质在肠道中不完全分解，被“漏肠”吸收，并在大脑中发挥“阿片样”作用。 D 'Eufemia在一小群自闭症儿童中报告了自闭症儿童肠道通透性增加的唯一支持证据（1）。 在一项对没有胃肠道症状的高功能自闭症儿童的研究中，D 'Eufemia等人发现21名儿童中有9名肠道通透性异常。尽管缺乏科学数据来支持无麸质和酪蛋白饮食，但许多家庭还是让孩子吃这种饮食。 这可能是因为自闭症没有治愈的方法。 这种饮食很难遵循，昂贵且耗时。准确的信息对自闭症儿童的家庭非常重要，这样他们就可以在充分知情的情况下决定对他们的孩子进行干预。 本研究将对肠道通透性进行更全面的评估。 将患有自闭症谱系障碍（ASD）的两组受试者与对照受试者进行比较。 将入组37例无麸质和酪蛋白饮食的ASD受试者和37例无限制饮食的受试者。 饮食不太可能影响肠道通透性，但麸质确实会增加乳糜泻患者的肠道通透性，因此两组将分别纳入。一组37人应具有足够的把握度，以检测组间的统计学显著差异。 这项研究将测试在乳糜泻中发现的血清自身抗体，乳糜泻是一种与肠道通透性增加和对麸质敏感性相关的小肠疾病。 乳糜泻可以是无症状的，可能发生在多达1%的一般人群中。 还将评价血清zonulin水平，因为zonulin与异常肠紧密连接相关，并可能影响肠通透性。 受试者将具有研究可靠的自闭症诊断，并将完成关于胃肠道症状的问卷调查，并保持7天的粪便记录。将招募37名具有典型发育的对照受试者，仅用于肠渗透性研究和问卷调查。仅当对照受试者的肠道通透性研究异常时，才对他们进行组织转氨酶采血。