Samsam Mohtashem, Ahangari Raheleh, Naser Saleh A
Mohtashem Samsam, Raheleh Ahangari, Saleh A Naser, Burnett School of Biomedical Sciences (BSBS), College of Medicine, University of Central Florida, Orlando, FL 32816, United States.
World J Gastroenterol. 2014 Aug 7;20(29):9942-51. doi: 10.3748/wjg.v20.i29.9942.
Autism spectrum disorders (ASD) comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors. Several genes have been implicated in the pathogenesis of ASD, most of them are involved in neuronal synaptogenesis. A number of environmental factors and associated conditions such as gastrointestinal (GI) abnormalities and immune imbalance have been linked to the pathophysiology of ASD. According to the March 2012 report released by United States Centers for Disease Control and Prevention, the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms. Although there is a strong genetic base for the disease, several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem. Many children suffering from ASD have GI problems such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, and intestinal infections. A number of studies focusing on the intestinal mucosa, its permeability, abnormal gut development, leaky gut, and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas. GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children. Maternal infection or autoimmune diseases have been suspected. Activation of the immune system during early development may have deleterious effect on various organs including the nervous system. In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.
自闭症谱系障碍（ASD）是一组始于幼儿期的神经发育异常疾病，其特征为社交沟通障碍以及包括兴趣受限和重复行为在内的行为问题。多种基因与ASD的发病机制有关，其中大多数参与神经元突触形成。一些环境因素及相关状况，如胃肠道（GI）异常和免疫失衡，已被认为与ASD的病理生理学有关。根据美国疾病控制与预防中心2012年3月发布的报告，近年来ASD的患病率急剧上升，现在每88名儿童中就有1名出现ASD症状。尽管该疾病有很强的遗传基础，但一些相关因素可能与ASD的发病机制直接相关，或作为基因的修饰因子从而加重初始问题。许多患有ASD的儿童存在胃肠道问题，如腹痛、慢性腹泻、便秘、呕吐、胃食管反流和肠道感染。一些针对肠黏膜、其通透性、肠道发育异常、肠漏及其他胃肠道问题的研究提出了许多问题，但研究结果在某种程度上尚无定论，美国儿科学会的一个专家小组强烈建议在这些领域进行进一步调查。胃肠道与免疫系统直接相关，ASD儿童通常会出现免疫反应失衡。人们怀疑母体感染或自身免疫性疾病与之有关。早期发育过程中免疫系统的激活可能会对包括神经系统在内的各种器官产生有害影响。在本综述中，我们简要回顾了胃肠道和免疫系统异常、神经肽失衡及其在ASD病理生理学中的作用，并讨论了一些未来的研究方向。
