Study of the Link Between Intestinal Dysbiosis and the Integrity of the Blood Brain Barrier in Autism
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Intestinal microbiota assessment
研究概览
简要总结
Autism Spectrum Disorder (ASD) is characterised by an impairment of social interactions and communication, associated with repetitive behaviour and restrictive interests. Clinical phenotypes of this neurodevelopmental disorder are heterogeneous and surprisingly up to 70% of ASD patients have gastro-intestinal (GI) disorders, associated with ASD severity and influence by feeding disorders.
Gut-brain axis seems to play a key role in neurodevelopment and ASD pathophysiology. Indeed an intestinal dysbiosis is observed in ASD, as well as intestinal inflammation and permeability. Aspecific inflammatory pattern suggests neuroinflammation processes in ASD. Neuroinflammation is involved in blood brain barrier (BBB) integrity and there are some arguments for a putative BBBimpairment in ASD. Nevertheless, no study has explored all together these parameters in ASD patients.
Here we hypothesise that intestinal dysbiosis in ASD could lead to a BBB impairment through neuroinflammation processes. Furthermore, this association between intestinal dysbiosis and BBB impairment could be influenced by a lot of clinical characteristics, such as ASD severity or GI disorders presence.
The principal aim of our study is to determine if the gut microbiota composition is associated with the BBB integrity in ASD. The secondary objectives are i) too identify in children with ASD some physiopathological pathways involved in this association, with a focus on associations betweenintestinal dysbiosis, intestinal permeability, intestinal permeability, the Th1/Th2 immune response, neuroinflammation and the BBB integrity; ii) to evaluate the influence of these associations on several clinical features of ASD such as ASD severity or GI disorders intensity; iii) to evaluate the influence of nutritional status on biological and clinical parameters.
This study will assess a lot of clinical and biological parameters together, some of them were never explored in ASD children. It will allow to better understand ASD pathophysiology, to highlight new therapeutic pathway, and to promote personalised medicine.
详细描述
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and communication, associated with repetitive behaviors and restricted interests. The pathophysiology of ASD is complex due to clinical heterogeneity and numerous comorbidities. Surprisingly, up to 70% of children with ASD have gastrointestinal (GI) disorders, correlated with the severity of ASD. These GI disorders are influenced by eating disorders linked to ASD. There is also an imbalance of the intestinal microbiota in ASD. In addition, the gut microbiota plays a key role in regulating the gut-brain axis. It is involved in brain development and neuroinflammation, one of the pathophysiological tracks in ASD. Neuroinflammation is also involved in regulating the integrity of the blood-brain barrier (BBB), which is affected in ASD. The question if intestinal dysbiosis influences the BBB integrity in ASD therefore arises.
The main objective is to determine if there is an association between the composition of the intestinal microbiota and the integrity of the BBB in ASD.
Secondary objectives are i/ to identify the pathophysiological pathways involved in this association, in particular via the neuroinflammation processes, ii/ to estimate the influence of this association on some ASD characteristics, iii/ to determine the influence of nutritional status on the measured biological and clinical parameters.
This is a monocentric, observational and cross-sectional study of 72 children with ASD, aged 6 to 16, living in the Languedoc-Roussillon region and from the ELENA cohort (this cohort includes 900 French children with an ASD, initially aged 2 to 16, and followed for 6 years).
Serum immunoassays will be assessed for the measurement of neuroinflammation, plasma assays for the intestinal inflammation and permeability. Clinical characteristics will be collected by a clinician and parental questionnaires (ASD severity test, level of social interaction, repetitive and stereotypical behavior, behavioral disorders, quality of life, intensity of GI disorders). Nutritional status will be assessed by serum metabolome analysis and anthropomorphic measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Intestinal microbiota assessment
时间窗: 9 months
At the end of the study, the analysis will be performed on all the samples at the same time by 16S RNAr pyrosequencing.
次要结局
- Measuring the severity of ASD(24 months)
- Evaluation of the level of social interaction(24 months)
- IQ (Intellectual Quotient)(24 months)
- Intensity of GI disorders(24 months)
- TH1/TH2 immune response(9 months)
- Behavioural disorders(24 months)
- Quality of life of children with ASD(24 months)
- Measurement of neuroinflammation(9 months)
- Developmental trajectory of children with ASD(24 months)
- Repetitive and stereotypical behaviours(24 months)
- Assessment of stools aspect(24 months)
- Intestinal permeability(9 months)
- Metabolome analysis(9 months)
- Intestinal inflammation(9 months)