INTESTINAL PERMEABILITY IN CHILDREN WITH AUTISM SPECTRUM DISORDERS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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，有许多免费和替代的治疗方法。据报道，自闭症谱系障碍儿童中有15%-20%出现胃肠道症状，许多关于自闭症病因的理论都源于胃肠道相关问题。根据“阿片类药物理论”，外行文献建议对自闭症儿童使用不含面筋和酪蛋白的饮食。在这一理论中，牛奶(酪蛋白)和小麦(面筋)蛋白质在肠道中不完全分解，被“渗漏的肠道”吸收，并在大脑中发挥“类阿片”作用。唯一支持自闭症儿童肠道通透性增加的证据是D‘Eufemia在一小部分自闭症儿童中报道的(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。尽管缺乏支持无面筋和酪蛋白饮食的科学数据，许多家庭还是让他们的孩子吃这种饮食。这可能是因为自闭症是无法治愈的。这种饮食很难遵守，价格昂贵，而且耗时。准确的信息对于自闭症儿童的家庭非常重要，这样他们就可以做出明智的决定，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。两组患有自闭症谱系障碍(ASD)的受试者将与对照组受试者进行比较。37名无面筋和酪蛋白饮食的自闭症患者和37名无限制饮食的自闭症患者将被纳入研究。饮食不太可能影响肠道通透性，但面筋确实会增加乳糜泻患者的肠道通透性，因此这两组将分别纳入。37个人的小组应该有足够的能力来检测小组之间的统计上的显著差异。这项研究将检测在乳糜泻中发现的血清自身抗体，这是一种与肠道通透性增加和对面筋敏感有关的小肠疾病。乳糜泻可以是无症状的，可能会发生在多达1%的总人口中。血清佐菌素水平也将被评估，因为佐菌素与异常的肠道紧密连接有关，并可能影响肠道通透性。受试者将有一个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天的大便记录。有典型发育的37名对照受试者将仅被招募进行肠道通透性研究和问卷调查。对照受试者只有在肠道通透性检查异常时才会抽血检测组织转谷氨酰胺酶

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 abnorm