Tight junctions, leaky intestines, and pediatric diseases.
ABSTRACT Tight junctions (TJs) represent the major barrier within the paracellular pathway between intestinal epithelial cells. Disruption of TJs leads to intestinal hyperpermeability (the so-called "leaky gut") and is implicated in the pathogenesis of several acute and chronic pediatric disease entities that are likely to have their origin during infancy.
This review provides an overview of evidence for the role of TJ breakdown in diseases such as systemic inflammatory response syndrome (SIRS), inflammatory bowel disease, type 1 diabetes, allergies, asthma, and autism.
A better basic understanding of this structure might lead to prevention or treatment of these diseases using nutritional or other means.
- SourceAvailable from: Stefanie NiederlechnerNutrition 05/2013; 29:1404–1411. · 3.05 Impact Factor
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ABSTRACT: Autism Spectrum Disorders are neurodevelopmental disorders with symptoms that include cognitive impairments, stereotyped behaviors, and impairments in social skills. The dramatic increase in incidence of autism in recent years has created an increased need to find effective treatments. This paper proposes a hypothesis for a systems model of the connections between Autism Spectrum Disorder pathogenesis routes observed in recent studies. A combination treatment option is proposed to combat multiple pathogenesis mechanisms at once. Autism has been cited as being linked to gastrointestinal symptoms and is thought to be caused by a combination of genetic predisposition and environmental factors. Neuroinflammation as a result of increased gastrointestinal permeability has been noted as being a likely cause of Autism Spectrum Disorders, with possible primary causes stemming from abnormal intestinal bacteria and/or sulfur metabolic deficiencies. Our pathogenesis model proposes a circular relationship: oxidative stress and sulfur metabolic deficiencies could cause changes in colonic bacterial composition; and environmental bacterial contaminants could lead to elevated oxidative stress in individuals. It would thus be a self-perpetuating process where treatment options with single targets would have short-lived effects. It is believed that bacterial toxins, oxidative stress and dietary allergens such as gluten could all lead to increased epithelial permeability. Therefore, we propose a combination treatment to combat intestinal permeability, abnormal bacteria and/or bacterial overgrowth, and sulfur metabolic deficiencies. It is our hope that the proposed model will inspire new studies in finding effective treatments for individuals with Autism Spectrum Disorders. We suggest possible future studies that may lend more credibility to the proposed model.Medical Hypotheses 12/2012; DOI:10.1016/j.mehy.2012.11.044 · 1.15 Impact Factor
Article: Environmental Factors in Autism[Show abstract] [Hide abstract]
ABSTRACT: Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.Frontiers in Psychiatry 01/2012; 3:118. DOI:10.3389/fpsyt.2012.00118