Kong Xuejun, Liu Jun, Liu Kevin, Koh Madelyn, Tian Ruiyi, Hobbie Clara, Fong Michelle, Chen Qiuyi, Zhao Minxuan, Budjan Christoph, Kong Jian
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street Charlestown, Boston, MA, 02129, USA.
Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
J Autism Dev Disord. 2021 Jan;51(1):144-157. doi: 10.1007/s10803-020-04524-1.
Autism spectrum disorder (ASD) is a complex neurological and developmental disorder, and a growing body of literature suggests the presence of autonomic nervous system (ANS) dysfunction in individuals with ASD. ANS is part of the "gut brain axis", which consists of an intricate interplay between the gut microbiome, mucosal immune system, enteric nervous system, ANS, and central processes receiving input from the vagus nerve. Measurements of the gut microbiome and the autonomic indices can serve as non-invasive markers of the status of the gut-brain axis in ASD. To our knowledge, no previous studies have explored the relationship between ANS and gut microbiome in individuals with ASD. Furthermore, while previous studies investigated the use of autonomic indices and gut microbiome independently as markers of ASD-related comorbidities, such as anxiety, cardiovascular issues, and gastrointestinal dysfunction, the use of combined autonomic indices and gut microbiome factors to classify ASD and control subjects has not been explored. In this study, we characterized autonomic function of a group of individuals with ASD in comparison to their paired, first-degree relative controls. Second, we explored the ASD gut-brain-axis through the relationship between gut microbiome markers and autonomic indices, as well as the correlation between the gut-brain-axis and clinical presentation of ASD. Lastly, this study explores the predictive capability of gut-brain-axis biomarkers (including autonomic and microbiome indices) in subtyping ASD cases, serving as a starting point to investigate the possibility of assisting in ASD screening and diagnosis that still heavily relies on psychological testing, which may be based on highly subjective standards.
自闭症谱系障碍(ASD)是一种复杂的神经和发育障碍,越来越多的文献表明,ASD患者存在自主神经系统(ANS)功能障碍。ANS是“肠脑轴”的一部分,肠脑轴由肠道微生物群、黏膜免疫系统、肠神经系统、ANS以及接受迷走神经输入的中枢过程之间的复杂相互作用组成。肠道微生物群和自主神经指标的测量可作为ASD患者肠脑轴状态的非侵入性标志物。据我们所知,之前没有研究探讨过ASD患者的ANS与肠道微生物群之间的关系。此外,虽然之前的研究分别调查了自主神经指标和肠道微生物群作为ASD相关合并症(如焦虑、心血管问题和胃肠功能障碍)标志物的用途,但尚未探讨将自主神经指标和肠道微生物群因素结合起来对ASD患者和对照受试者进行分类的用途。在本研究中,我们对一组ASD患者及其配对的一级亲属对照的自主神经功能进行了表征。其次,我们通过肠道微生物群标志物与自主神经指标之间的关系以及肠脑轴与ASD临床表现之间的相关性,探索了ASD的肠脑轴。最后,本研究探讨了肠脑轴生物标志物(包括自主神经和微生物群指标)在ASD病例亚型分类中的预测能力,作为研究协助ASD筛查和诊断可能性的起点,目前ASD筛查和诊断仍严重依赖心理测试,而心理测试可能基于高度主观的标准。