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Brain Behav Immun. 2018 May;70:354-368. doi: 10.1016/j.bbi.2018.03.025. Epub 2018 Mar 20.

Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms.

Author information

1
Department of Medical Microbiology and Immunology, University of California Davis, USA; MIND Institute, University of California Davis, USA.
2
Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, MassGeneral Hospital for Children, Boston, MA, USA; Graduate Program in Life Sciences University of Maryland School of Medicine, Baltimore, MD, USA.
3
Institute of Genomic Science, University of Maryland School of Medicine, Baltimore, MD, USA.
4
MIND Institute, University of California Davis, USA; Department of Pediatrics, University of California Davis, USA; Children's Center for Environmental Health, University of California Davis, CA, USA.
5
Children's Center for Environmental Health, University of California Davis, CA, USA; Public Health Sciences, University of California Davis, CA, USA.
6
MIND Institute, University of California Davis, USA; Children's Center for Environmental Health, University of California Davis, CA, USA; Public Health Sciences, University of California Davis, CA, USA.
7
MIND Institute, University of California Davis, USA; Children's Center for Environmental Health, University of California Davis, CA, USA; Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, CA, USA.
8
Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, MassGeneral Hospital for Children, Boston, MA, USA.
9
Department of Medical Microbiology and Immunology, University of California Davis, USA; MIND Institute, University of California Davis, USA; Children's Center for Environmental Health, University of California Davis, CA, USA. Electronic address: pashwood@ucdavis.edu.

Abstract

OBJECTIVES:

Many studies have reported the increased presence of gastrointestinal (GI) symptoms in children with autism spectrum disorders (ASD). Altered microbiome profiles, pro-inflammatory responses and impaired intestinal permeability have been observed in children with ASD and co-morbid GI symptoms, yet few studies have compared these findings to ASD children without GI issues or similarly aged typical developing children. The aim of this study was to determine whether there are biological signatures in terms of immune dysfunction and microbiota composition in children with ASD with GI symptoms.

METHODS:

Children were enrolled in one of four groups: ASD and GI symptoms of irregular bowel habits (ASDGI), children with ASD but without current or previous GI symptoms (ASDNoGI), typically developing children with GI symptoms (TDGI) and typically developing children without current or previous GI symptoms (TDNoGI). Peripheral blood mononuclear cells (PBMC) were isolated from the blood, stimulated and assessed for cytokine production, while stool samples were analyzed for microbial composition.

RESULTS:

Following Toll-Like receptor (TLR)-4 stimulation, the ASDGI group produced increased levels of mucosa-relevant cytokines including IL-5, IL-15 and IL-17 compared to ASDNoGI. The production of the regulatory cytokine TGFβ1 was decreased in the ASDGI group compared with both the ASDNoGI and TDNoGI groups. Analysis of the microbiome at the family level revealed differences in microbiome composition between ASD and TD children with GI symptoms; furthermore, a predictive metagenome functional content analysis revealed that pathways were differentially represented between ASD and TD subjects, independently of the presence of GI symptoms. The ASDGI also showed an over-representation of the gene encoding zonulin, a molecule regulating gut permeability, compared to the other groups.

CONCLUSIONS:

Overall our findings suggest that children with ASD who experience GI symptoms have an imbalance in their immune response, possibly influenced by or influencing metagenomic changes, and may have a propensity to impaired gut barrier function which may contribute to their symptoms and clinical outcome.

KEYWORDS:

ASD; Autism; Cytokines; Gastrointestinal; Immune; Microbiota; Mucosal Immunity; Zonulin

PMID:
29571898
PMCID:
PMC5953830
DOI:
10.1016/j.bbi.2018.03.025
[Indexed for MEDLINE]
Free PMC Article

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