PreprintCited by 44Gut microbiota and healthAutism Spectrum Disorder ResearchGastrointestinal motility and disorders

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Microbiome-Gut-Mucosal-Immune-Brain Axis and Autism Spectrum Disorder (ASD): A Novel Proposal of the Role of Gut Microbiome in ASD Aetiology

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De Sales-Millán, Amapola, Aguirre-Garrido, José Félix, González-Cervantes, Rina María, Velázquez-Aragón, Jose Antonio·2023·Behavioral Sciences

DOI 10.20944/preprints202305.1223.v1PMC PMC10376175

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Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by poor social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome-gut-brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders, and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function, and microbiota metabolites in ASD. Although a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity, and the microbiome-gut-brain axis in the development of autistic symptoms severity and, a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via microbiome-gut-brain axis in a feedback circuit.

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Figure 1 Vicious cycle and phenotype relationship in ASD.CC BY · PubMed Central

Figure 2 Microbiome–Gut–Mucosal–Immune–Brain bidirectional relationship. The vagus nerve transfers information on the state of the digestive system to the brain through sensory fibres. It sends neuronal, endocrine and immune signals. The gut microbiota metabolites are involved in permeability of the intestinal epithelium, neurotransmitter synthesis and cytokines release. (A) Homeostasis. Under homeostasis conditions, gut microbiome and diet control the activity of ENS cells through SCFA, which in turn activate the enteroendocrine cells of the intestinal epithelium, which increases the production of serotonin and therefore changes intestinal motility. In addition, the microbiome is essential for the maintenance of mucosal glial cells that express neurotrophic factor. (B) Dysbiosis. The imbalance in the homeostasis of the gut microbiome is associated with the decreased production of metabolites, such as butyrate, responsible for the modulation of inhibitory and excitatory pathways, and with anti-inflammatory effects on microglia. Deficiency of this microbial metabolite could be the cause of a disruption in the intercommunication between the ENS and the mucosal immune system.CC BY · PubMed Central

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Authors: De Sales-Millán, A., Aguirre-Garrido, J. F., González-Cervantes, R. M., & Velázquez-Aragón, J. A.
ORCID: De Sales-Millán, Amapola
Aguirre-Garrido, José Félix
González-Cervantes, Rina María
Velázquez-Aragón, Jose Antonio
Venue: Behavioral Sciences
Publisher: MDPI AG
Published: 2023-05-17
Volume: 13
Issue: 7
Pages: 548-548
ISSN: 2076-328X (ISSN-L)
DOI: 10.20944/preprints202305.1223.v1
PMC: PMC10376175
OpenAlex: W4382983015
Cited by: 44
References: 166
Citations by year: 2026: 15 · 2025: 17 · 2024: 11 · 2023: 1
FWCI: 1.16
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Behavioral Sciences (publishedVersion, cc-by)
Preprints.org (acceptedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Instituto Nacional de Pediatria (Recursos Fiscales 2022-2023)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: autism spectrum disorder, gut microbiota, microbiome-gut-brain axis, gut dysbiosis, intestinal permeability, immune function, microbial diversity, gastrointestinal diseases, microbiota metabolites, neurodevelopmental disorders

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Microbiome-Gut-Mucosal-Immune-Brain Axis and Autism Spectrum Disorder (ASD): A Novel Proposal of the Role of Gut Microbiome in ASD Aetiology

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