首页> 美国卫生研究院文献>Microbial Ecology in Health and Disease >Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome
【2h】

Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome

机译:自闭症谱系障碍中的胃肠道功能障碍:线粒体和肠道微生物组的作用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Autism spectrum disorder (ASD) affects a significant number of individuals worldwide with the prevalence continuing to grow. It is becoming clear that a large subgroup of individuals with ASD demonstrate abnormalities in mitochondrial function as well as gastrointestinal (GI) symptoms. Interestingly, GI disturbances are common in individuals with mitochondrial disorders and have been reported to be highly prevalent in individuals with co-occurring ASD and mitochondrial disease. The majority of individuals with ASD and mitochondrial disorders do not manifest a primary genetic mutation, raising the possibility that their mitochondrial disorder is acquired or, at least, results from a combination of genetic susceptibility interacting with a wide range of environmental triggers. Mitochondria are very sensitive to both endogenous and exogenous environmental stressors such as toxicants, iatrogenic medications, immune activation, and metabolic disturbances. Many of these same environmental stressors have been associated with ASD, suggesting that the mitochondria could be the biological link between environmental stressors and neurometabolic abnormalities associated with ASD. This paper reviews the possible links between GI abnormalities, mitochondria, and ASD. First, we review the link between GI symptoms and abnormalities in mitochondrial function. Second, we review the evidence supporting the notion that environmental stressors linked to ASD can also adversely affect both mitochondria and GI function. Third, we review the evidence that enteric bacteria that are overrepresented in children with ASD, particularly Clostridia spp., produce short-chain fatty acid metabolites that are potentially toxic to the mitochondria. We provide an example of this gut–brain connection by highlighting the propionic acid rodent model of ASD and the clinical evidence that supports this animal model. Lastly, we discuss the potential therapeutic approaches that could be helpful for GI symptoms in ASD and mitochondrial disorders. To this end, this review aims to help better understand the underlying pathophysiology associated with ASD that may be related to concurrent mitochondrial and GI dysfunction.
机译:自闭症谱系障碍(ASD)影响全球范围内的大量个体,且患病率持续增长。越来越明显的是,一大群患有ASD的个体表现出线粒体功能异常以及胃肠道(GI)症状。有趣的是,胃肠道疾病在线粒体疾病患者中很常见,据报道在同时发生的ASD和线粒体疾病患者中普遍存在。大多数患有ASD和线粒体疾病的个体没有表现出原发性遗传突变,这增加了他们的线粒体疾病获得性遗传的可能性,或者至少是由遗传易感性与广泛的环境触发因素共同作用导致的。线粒体对内源性和外源性环境压力非常敏感,例如有毒物,医源性药物,免疫激活和代谢紊乱。这些相同的环境应激源中有许多都与ASD相关,这表明线粒体可能是环境应激源与ASD相关的神经代谢异常之间的生物学联系。本文回顾了胃肠道异常,线粒体和自闭症之间的可能联系。首先,我们回顾了胃肠道症状与线粒体功能异常之间的联系。其次,我们回顾了支持以下观点的证据,即与ASD相关的环境应激因素也可能对线粒体和胃肠功能产生不利影响。第三,我们回顾了证据,表明在ASD儿童(尤其是梭状芽胞杆菌)中过量存在的肠细菌会产生可能对线粒体有毒的短链脂肪酸代谢产物。我们通过强调ASD的丙酸啮齿动物模型和支持该动物模型的临床证据,提供了这种肠脑连接的例子。最后,我们讨论了可能对ASD和线粒体疾病的胃肠道症状有帮助的潜在治疗方法。为此,本综述旨在帮助更好地了解与ASD相关的潜在病理生理,该病理可能与并发线粒体和GI功能障碍有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号