Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
Open accessAbstract
Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD) but the pathophysiology is poorly understood.Imbalances in the enteric microbiome have been associated with ASD and can cause GI dysfunction potentially through disruption of mitochondrial function as microbiome metabolites modulate mitochondrial function and mitochondrial dysfunction is highly associated with GI symptoms.In this study, we compared mitochondrial function in rectal and cecum biopsies under the assumption that certain microbiome metabolites, such as butyrate and propionic acid, are more abundant in the cecum as compared to the rectum.Rectal and cecum mucosal biopsies were collected during elective diagnostic colonoscopy.Using a single-blind case-control design, complex I and IV and citrate synthase activities and complex I-V protein quantity from 10 children with ASD, 10 children with Crohn's disease and 10 neurotypical children with nonspecific GI complaints were measured.The protein for all complexes, except complex II, in the cecum as compared to the rectum was significantly higher in ASD samples as compared to other groups.For both rectal and cecum biopsies, ASD samples demonstrated higher complex I activity, but not complex IV or citrate synthase activity, compared to other groups.Mitochondrial function in the gut mucosa from children with ASD was found to be significantly different than other groups who manifested similar GI symptomatology suggesting a unique pathophysiology for GI symptoms in children with ASD.Abnormalities localized to the cecum suggest a role for imbalances in the microbiome, potentially in the production of butyrate, in children with ASD. BackgroundAutism Spectrum Disorder (ASD) is characterized by impairments in communication and social interactions along with restrictive and repetitive behaviors [1].In the United States, ASD is now estimated to affect almost 2% of children [2].Although behaviorally defined, ASD is associated with several medical co-morbidities [3] such as allergies [4], epilepsy [5],
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Gut microbiota-derived short-chain fatty acids such as propionic acid and butyric acid have immunomodulatory properties.
“Furthermore, gut microbiota-derived short-chain fatty acids (SCFAs), such as propionic acid [69, 70] and butyric acid [71, 72], produced by bacterial fermentation of carbohydrates have immunomodulatory properties”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [72]
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- Authors
- Rose, S., Bennuri, S. C., Murray, K. F., Buie, T., Winter, H., & Frye, R. E.
- Affiliations
- Arkansas Children's Research Institute (US)
- Massachusetts General Hospital (US)
- Boston Children's Hospital (US)
- Corresponding author
- Frye, Richard Eugene
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-10-13
- Volume
- 12
- Issue
- 10
- Pages
- e0186377
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5640251
- OpenAlex
- W2762265991
- Cited by
- 82
- References
- 84
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 16 · 2021: 13 · 2020: 12 · 2019: 8 · 2018: 10
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Arkansas Biosciences Institute
- Autism Research Institute
- Martin Schlaff
- 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, mitochondrial dysfunction, gastrointestinal symptoms, gut microbiota, cecal mucosa, rectal mucosa, complex I, cytochrome c oxidase, citrate synthase, butyrate, propionic acid, Crohn's disease, children
- MeSH terms
- Adolescent, Autistic Disorder, Child, Female, Humans, Male, Case-Control Studies, Gastrointestinal Tract, Electron Transport Chain Complex Proteins
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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