The Gut-Immune-Brain Axis in Autism Spectrum Disorders; A Focus on Amino Acids
Open accessAbstract
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that affect communication and social behavior. Besides social deficits, systemic inflammation, gastrointestinal immune-related problems, and changes in the gut microbiota composition are characteristic for people with ASD. Animal models showed that these characteristics can induce ASD-associated behavior, suggesting an intimate relationship between the microbiota, gut, immune system and the brain in ASD. Multiple factors can contribute to the development of ASD, but mutations leading to enhanced activation of the mammalian target of rapamycin (mTOR) are reported frequently. Hyperactivation of mTOR leads to deficits in the communication between neurons in the brain and to immune impairments. Hence, mTOR might be a critical factor linking the gut-brain-immune axis in ASD. Pharmacological inhibition of mTOR is shown to improve ASD-associated behavior and immune functions, however, the clinical use is limited due to severe side reactions. Interestingly, studies have shown that mTOR activation can also be modified by nutritional stimuli, in particular by amino acids. Moreover, specific amino acids are demonstrated to inhibit inflammation, improve gut barrier function and to modify the microbiota composition. In this review we will discuss the gut-brain-immune axis in ASD and explore the potential of amino acids as a treatment option for ASD, either via modification of mTOR activity, the immune system or the gut microbiota composition.
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The gut microbiome likely alters brain functions through various mechanisms including environmental factors, host genetics, host immune response regulation, excretion of metabolites, regulation of neurotransmitters, or neuroactive compounds.
“the gut microbiome likely alters brain functions through various other mechanisms, including environmental factors (e.g. in utero exposure to infection, maternal conditions, and medications), host genetics, host immune response regulation [12, 57, 58], excretion of metabolites such as tyrosine analogues, p-cresol, 4-ethylphenylsulfate, indoles, lipopolysaccharides and free amino acids [59-62],”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [58]
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Novel Personalized Dietary Treatment for Autism Based on the Gut-Immune-Endocrine-Brain Axis
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Cited by
Sorted by citations
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- Authors
- van Sadelhoff, J. H. J., Perez Pardo, P., Wu, J., Garssen, J., van Bergenhenegouwen, J., Hogenkamp, A., Hartog, A., & Kraneveld, A. D.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Utrecht University (NL)
- Corresponding author
- Kraneveld, Aletta D.
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2019-04-16
- Volume
- 10
- Pages
- 247-247
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC6477881
- OpenAlex
- W2940286118
- Cited by
- 71
- References
- 195
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 11 · 2021: 20 · 2020: 10 · 2019: 4
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Universiteit Utrecht
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, gut-brain-immune axis, amino acids, mTOR hyperactivation, gut microbiota, systemic inflammation, intestinal barrier, nutritional therapy, mTOR inhibition, neurodevelopmental disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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