Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies
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Introduction: Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT). Methods: We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design. Results: Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with Faecalibacterium (phylum Firmicutes) and positively correlated with Bacteroides sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with Lactobacillus sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of Lactobacillus sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities’ composition. Discussion: Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior. Systematic review registration: https://clinicaltrials.gov/ , CRD42020158734.
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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 [92]
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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?
Zarimeidani, F., Rahmati, R., Mostafavi, M., Darvishi, M., Khodadadi, S., Mohammadi, M., Shamlou, F., Bakhtiyari, S., & Alipourfard, I. (2024) · Inflammation · doi:10.1007/s10753-024-02061-y · Cited by 47 · see citing works
- Authors
- Caputi, V., Hill, L., Figueiredo, M., Popov, J., Hartung, E., Margolis, K. G., Baskaran, K., Joharapurkar, P., Moshkovich, M., & Pai, N.
- Affiliations
- Agricultural Research Service (US)
- McGill University Health Centre (CA)
- University of Toronto (CA)
- Boston Children's Hospital (US)
- McMaster University (CA)
- New York University (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Caputi, Valentina
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2024-03-07
- Volume
- 18
- Pages
- 1341656-1341656
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC10954784
- OpenAlex
- W4392559785
- Cited by
- 41
- References
- 136
- Citations by year
- 2026: 17 · 2025: 14 · 2024: 10
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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
- gut microbiota, autism spectrum disorder, attention deficit hyperactivity disorder, Rett syndrome, neurodevelopmental disorders, Firmicutes/Bacteroidetes ratio, short-chain fatty acids, inflammatory cytokines, neurotransmitters, constipation, visceral pain, hyperactivity/impulsivity, Faecalibacterium, Bacteroides, probiotics, Lactobacillus, fecal microbiota transplantation, micronutrient supplementation, gut-brain axis
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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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