Intestinal Barrier Dysfunction and Microbiota–Gut–Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder
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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multifactorial etiology, characterized by impairment in two main functional areas: (1) communication and social interactions, and (2) skills, interests and activities. ASD patients often suffer from gastrointestinal symptoms associated with dysbiotic states and a “leaky gut.” A key role in the pathogenesis of ASD has been attributed to the gut microbiota, as it influences central nervous system development and neuropsychological and gastrointestinal homeostasis through the microbiota–gut–brain axis. A state of dysbiosis with a reduction in the Bacteroidetes/Firmicutes ratio and Bacteroidetes level and other imbalances is common in ASD. In recent decades, many authors have tried to study and identify the microbial signature of ASD through in vivo and ex vivo studies. In this regard, the advent of metabolomics has also been of great help. Based on these data, several therapeutic strategies, primarily the use of probiotics, are investigated to improve the symptoms of ASD through the modulation of the microbiota. However, although the results are promising, the heterogeneity of the studies precludes concrete evidence. The aim of this review is to explore the role of intestinal barrier dysfunction, the gut–brain axis and microbiota alterations in ASD and the possible role of probiotic supplementation in these patients.
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The most notable alterations in ASD gut microbiota include different prevalences of Bacteroidetes/Firmicutes, Bifidobacterium, Faecalibacterium, Clostridium, Enterobacteriaceae, Verrucomicrobia, Fusobacteria, Escherichia coli, Lactobacillus, Streptococcus, Enterococcus, Prevotella, and Akkermansia.
“The most notable alterations included the different prevalences of Bacteroidetes/Firmicutes, Bifidobacterium, Faecalibacterium, Clostridium, Enterobacteriaceae, Verrucomicrobia, Fusobacteria, Escherichia coli, Lactobacillus, Streptococcus, Enterococcus, Prevotella, and Akkermansia.”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [89]
The excitatory glutamate pathway appears to contribute to the etiopathogenesis of ASD by functioning as part of the gut-brain axis and facilitating trans-synaptic signaling.
“Additionally, the excitatory glutamate pathway appears to contribute to the etiopathogenesis of ASD by functioning as part of the gut–brain axis and facilitating trans-synaptic signaling [89].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [89]
The presence of Alistipes may be observed at elevated levels in patients diagnosed with ASD.
“Furthermore, the presence of Alistipes may be observed at elevated levels in patients diagnosed with ASD [50,89,96,97,98].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [89]
The abundance of the genus Faecalibacterium, particularly the species Faecalibacterium prausnitzii, should be lower in healthy individuals compared to patients diagnosed with ASD.
“It was also observed that the abundance of the genus Faecalibacterium, particularly the Faecalibacterium prausnitzii species, should be lower in healthy individuals compared to patients diagnosed with ASD [52,89,101,107,109,113].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [89]
A multitude of scientific studies have reported a potential decrease in the abundance of Bifidobacterium in individuals diagnosed with ASD.
“A multitude of scientific studies have reported a potential decrease in the abundance of Bifidobacterium in individuals diagnosed with ASD [52,89,101,102,103,106,107,113].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [89]
A decrease in the populations of Akkermansia and Sutterella, with particular emphasis on Akkermansia muciniphila, was observed in healthy controls.
“Moreover, a decrease in the populations of Akkermansia and Sutterella, with a particular emphasis on Akkermansia muciniphila species, was observed in healthy controls [52,89,107,109,110].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [89]
The potential of interventions targeting the gut microbiome to alleviate ASD symptoms and address coexisting gastrointestinal issues arises from the microbiota's ability to modulate inflammation.
“Initial research on the influence of the microbiota on ASD suggest that interventions targeting the gut microbiome may provide a promising approach for alleviating symptoms and addressing coexisting gastrointestinal issues. This potential arises from the microbiota’s ability to modulate inflammation [89].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [89]
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The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders
Młynarska, E., Barszcz, E., Budny, E., Gajewska, A., Kopeć, K., Wasiak, J., Rysz, J., & Franczyk, B. (2025) · Nutrients · doi:10.3390/nu17071135 · Cited by 44 · see citing works
Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?
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- Authors
- Dargenio, V. N., Dargenio, C., Castellaneta, S., De Giacomo, A., Laguardia, M., Schettini, F., Francavilla, R., & Cristofori, F.
- Affiliations
- Ospedale Pediatrico Giovanni XXIII (IT)
- Child Neuropsychiatry Unit, Department of Translational Biomedicine and Neuroscience, University of Bari “Aldo Moro”, 70126 Bari, Italy
- University of Bari Aldo Moro (IT)
- Corresponding author
- Francavilla, Ruggiero
- ORCID
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2023-03-27
- Volume
- 15
- Issue
- 7
- Pages
- 1620
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC10096948
- OpenAlex
- W4361004093
- Cited by
- 98
- References
- 218
- Citations by year
- 2026: 27 · 2025: 38 · 2024: 29 · 2023: 4
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by)
- 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, intestinal barrier dysfunction, microbiota-gut-brain axis, gut dysbiosis, leaky gut, Firmicutes/Bacteroidetes ratio, gastrointestinal symptoms, probiotics, metabolomics, microbial signatures, ASD pathogenesis
- MeSH terms
- Autism Spectrum Disorder, Gastrointestinal Microbiome, Brain-Gut Axis, Gastrointestinal Diseases, Humans, Intestinal Diseases, Probiotics, Microbiota, Dysbiosis
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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.
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