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Cited by 201Autism Spectrum Disorder ResearchChild Nutrition and Feeding IssuesFood Allergy and Anaphylaxis Research

Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention

Jyonouchi, Harumi, Geng, Lee, Ruby, Agnes, Zimmerman-Bier, Barbie·2005·Neuropsychobiology
DOI 10.1159/000084164
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Abstract

Objective: Our previous study indicated an association between cellular immune reactivity to common dietary proteins (DPs) and excessive proinflammatory cytokine production with endotoxin (lipopolysaccharide, LPS), a major stimulant of innate immunity in the gut mucosa, in a subset of autism spectrum disorder (ASD) children. However, it is unclear whether such abnormal LPS responses are intrinsic in these ASD children or the results of chronic gastrointestinal (GI) inflammation secondary to immune reactivity to DPs. This study further explored possible dysregulated production of proinflammatory and counter-regulatory cytokines with LPS in ASD children and its relationship to GI symptoms and the effects of dietary intervention measures. Methods: This study includes ASD children (median age 4.8 years) on the unrestricted (n = 100) or elimination (n = 77) diet appropriate with their immune reactivity. Controls include children with non-allergic food hypersensitivity (NFH; median age 2.9 years) on the unrestricted (n = 14) or elimination (n = 16) diet, and typically developing children (median age 4.5 years, n = 13). The innate immune responses were assessed by measuring production of proinflammatory (TNF-α, IL-1β, IL-6, and IL-12) and counter-regulatory (IL-1ra, IL-10, and sTNFRII) cytokines by peripheral blood mononuclear cells (PBMCs) with LPS. The results were also compared to T-cell responses with common DPs and control T-cell mitogens assessed by measuring T-cell cytokine production. Results: ASD and NFH PBMCs produced higher levels of TNF-α with LPS than controls regardless of dietary interventions. However, only in PBMCs from ASD children with positive gastrointestinal (GI(+)) symptoms, did we find a positive association between TNF-α levels produced with LPS and those with cow’s milk protein (CMP) and its major components regardless of dietary interventions. In the unrestricted diet group, GI(+) ASD PBMCs produced higher IL-12 than controls and less IL-10 than GI(–) ASD PBMCs with LPS. GI(+) ASD but not GI(–) ASD or NFH PBMCs produced less counter-regulatory cytokines with LPS in the unrestricted diet group than in the elimination diet group. There was no significant difference among the study groups with regard to cytokine production in responses to T-cell mitogens and other recall antigens. Conclusion: Our results revealed that there are findings limited to GI(+) ASD PBMCs in both the unrestricted and elimination diet groups. Thus our findings indicate intrinsic defects of innate immune responses in GI(+) ASD children but not in NFH or GI(–) ASD children, suggesting a possible link between GI and behavioral symptoms mediated by innate immune abnormalities.

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Crossref · 10.1159/000084164

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  • PBMCs from children with ASD produce higher levels of TNF-α and IFN-γ but not IL-5, lending credence to a Th1-dominated response.

    “In the context of dietary proteins and food hypersensitivity, PBMCs from children with ASD produce higher levels of TNF-α and IFN-γ but not IL-5, further lending credence to a Th1-dominated response (Jyonouchi et al, 2005;Jyonouchi et al, 2002).”

    From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Jyonouchi et al, 2005

  • Our results are in agreement with previous findings of elevated TNF-α expression in children with ASD and GI symptoms compared to non-inflamed controls that was similar to participants with Crohn's disease.

    “Our results are in agreement with previous findings of elevated TNF-α expression in children with ASD and GI symptoms [87] compared to non-inflamed controls that was similar to participants with Crohn’s disease [22].”

    From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [87]

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Authors
Jyonouchi, H., Geng, L., Ruby, A., & Zimmerman-Bier, B.
Affiliations
Rutgers New Jersey Medical School (US)
Venue
Neuropsychobiology
Publisher
S. Karger AG
Published
2005
Volume
51
Issue
2
Pages
77-85
ISSN
  • 0302-282X (ISSN-L)
  • 1423-0224
DOI
10.1159/000084164
OpenAlex
W2139677234
Cited by
201
References
25
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 11 · 2017: 6 · 2016: 10 · 2015: 10 · 2014: 7 · 2013: 14 · 2012: 13
FWCI
5.93
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Neuropsychobiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
  • Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
Keywords
autism spectrum disorder, innate immunity, lipopolysaccharide, inflammatory cytokines, TNF-α, IL-12, IL-10, cow's milk protein, gastrointestinal symptoms, peripheral blood mononuclear cells, T cell response, children, intestinal mucosa, immune dysregulation
MeSH terms
Autistic Disorder, Child, Child, Preschool, Diet, Dietary Proteins, Enzyme-Linked Immunosorbent Assay, Food Hypersensitivity, Gastrointestinal Diseases, Humans, Immunity, Infant, Lactoglobulins, Lipopolysaccharides, Monocytes, T-Lymphocytes, Cytokines, In Vitro Techniques

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