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Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis

1
Unit for Nutrition Research, Faculty of Food and Nutritional Sciences, University of Iceland, 101 Reykjavik, Iceland
2
Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland
3
Department of Child and Adolescent Psychiatry, Landspitali University Hospital, 101 Reykjavik, Iceland
4
Division of Pediatric Gastroenterology and Nutrition, Harvard Medical School, MassGeneral Hospital for Children, Boston, MA 02114, USA
5
Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland
6
Department of Scientific Affairs, Landspitali University Hospital, 101 Reykjavik, Iceland
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(7), 1982; https://doi.org/10.3390/nu12071982
Received: 6 June 2020 / Revised: 29 June 2020 / Accepted: 1 July 2020 / Published: 3 July 2020
(This article belongs to the Special Issue Nutrient Targeting of Intestinal Mucosa Wall to Modulate Metabolism)
Worldwide, up to 20% of children and adolescents experience mental disorders, which are the leading cause of disability in young people. Research shows that serum zonulin levels are associated with increased intestinal permeability (IP), affecting neural, hormonal, and immunological pathways. This systematic review and meta-analysis aimed to summarize evidence from observational studies on IP in children diagnosed with mental disorders. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the Cochrane Library, PsycINFO, PubMed, and the Web of Science identified 833 records. Only non-intervention (i.e., observational) studies in children (<18 years) diagnosed with mental disorders, including a relevant marker of intestinal permeability, were included. Five studies were selected, with the risk of bias assessed according to the Newcastle–Ottawa scale (NOS). Four articles were identified as strong and one as moderate, representing altogether 402 participants providing evidence on IP in children diagnosed with attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive–compulsive disorder (OCD). In ADHD, elevated serum zonulin levels were associated with impaired social functioning compared to controls. Children with ASD may be predisposed to impair intestinal barrier function, which may contribute to their symptoms and clinical outcome compared to controls. Children with ASD, who experience gastro-intestinal (GI) symptoms, seem to have an imbalance in their immune response. However, in children with OCD, serum zonulin levels were not significantly different compared to controls, but serum claudin-5, a transmembrane tight-junction protein, was significantly higher. A meta-analysis of mean zonulin plasma levels of patients and control groups revealed a significant difference between groups (p = 0.001), including the four studies evaluating the full spectrum of the zonulin peptide family. Therefore, further studies are required to better understand the complex role of barrier function, i.e., intestinal and blood–brain barrier, and of inflammation, to the pathophysiology in mental and neurodevelopmental disorders. This review was PROSPERO preregistered, (162208). View Full-Text
Keywords: children; adolescents; intestinal permeability; mental disorders; zonulin; haptoglobin; attention deficit and hyperactivity disorder (ADHD); autism spectrum disorder (ASD); obsessive–compulsive disorder (OCD); systematic review; meta-analysis children; adolescents; intestinal permeability; mental disorders; zonulin; haptoglobin; attention deficit and hyperactivity disorder (ADHD); autism spectrum disorder (ASD); obsessive–compulsive disorder (OCD); systematic review; meta-analysis
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Asbjornsdottir, B.; Snorradottir, H.; Andresdottir, E.; Fasano, A.; Lauth, B.; Gudmundsson, L.S.; Gottfredsson, M.; Halldorsson, T.I.; Birgisdottir, B.E. Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis. Nutrients 2020, 12, 1982.

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