The manifestations of autism spectrum disorder (ASD) are highly heterogeneous. As many individuals with ASD have gastrointestinal (GI) comorbidities, ASD with GI problems is considered to be a subtype of ASD. Vitamin A (VA) plays an important role in the development of both the central and peripheral nervous system. However, the relationship between VA deficiency (VAD) and ASD with GI comorbidities is still unclear. We established rat models with different VA levels based on the valproic acid-induced autism model. Compared to autism model rats with VA normal (VAN), autism model rats with gestational VAD showed more severe autism-like behavior, increased GI transit time, and impairment of the enteric nervous system (ENS). Besides, the expression levels of retinoic acid receptor α (RARα) and Ret in autism model rats with VAD were decreased compared with those in rats with VAN. Supplementation with VA was found to effectively ameliorate autism-like behaviors and impairments of GI motility and the ENS in autism model rats with VAD. Chromatin immunoprecipitation results suggested that RARa can bind to the promoter region of the Ret gene and regulate the Ret signaling pathway. We speculate that VAD in autism might lead to impairments of both the brain and ENS. VAD might be a factor that causes individuals to be more susceptible to ASD-related risk factors and aggravates a subtype of ASD with GI comorbidities.

自闭症谱系障碍（ASD）的表现高度异质。由于许多患有ASD的人患有胃肠道（GI）合并症，因此患有GI问题的ASD被认为是ASD的一种亚型。维生素A（VA）在中枢神经系统和周围神经系统的发育中起着重要作用。但是，VA缺乏症（VAD）和ASD与GI合并症之间的关系仍不清楚。我们基于丙戊酸诱发的自闭症模型建立了具有不同VA水平的大鼠模型。与具有VA正常（VAN）的自闭症模型大鼠相比，具有妊娠VAD的自闭症模型大鼠表现出更严重的自闭症样行为，GI传递时间增加和肠神经系统（ENS）受损。除了，VAD自闭症模型大鼠视黄酸受体α（RARα）和Ret的表达水平较VAN大鼠降低。发现补充VA可以有效改善自闭症模型大鼠VAD中的自闭症样行为以及胃肠动力和ENS的损害。染色质的免疫沉淀结果表明，RARa可以结合Ret基因的启动子区域并调节Ret信号通路。我们推测自闭症中的VAD可能导致大脑和ENS的损伤。VAD可能是导致个体更易患ASD相关危险因素并加重GI合并症的ASD亚型的因素。发现补充VA可以有效改善自闭症模型大鼠VAD中的自闭症样行为以及胃肠动力和ENS的损害。染色质的免疫沉淀结果表明RARa可以结合Ret基因的启动子区域并调节Ret信号通路。我们推测自闭症中的VAD可能导致大脑和ENS的损伤。VAD可能是导致个体更易患ASD相关危险因素并加重GI合并症的ASD亚型的因素。发现补充VA可以有效改善自闭症模型大鼠VAD中的自闭症样行为以及胃肠动力和ENS的损害。染色质的免疫沉淀结果表明RARa可以结合Ret基因的启动子区域并调节Ret信号通路。我们推测自闭症中的VAD可能会导致大脑和ENS的损伤。VAD可能是导致个体更易患ASD相关危险因素并加重GI合并症的ASD亚型的因素。