Cited by 130Gut microbiota and healthAutism Spectrum Disorder ResearchMitochondrial Function and Pathology

Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines

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Frye, R E, Rose, S, Chacko, J, Wynne, R, Bennuri, S C, Slattery, J C, Tippett, M, Delhey, L +3 more·2016·Translational Psychiatry

Abstract

Propionic acid (PPA) is a ubiquitous short-chain fatty acid, which is a major fermentation product of the enteric microbiome. PPA is a normal intermediate of metabolism and is found in foods, either naturally or as a preservative. PPA and its derivatives have been implicated in both health and disease. Whereas PPA is an energy substrate and has many proposed beneficial effects, it is also associated with human disorders involving mitochondrial dysfunction, including propionic acidemia and autism spectrum disorders (ASDs). We aimed to investigate the dichotomy between the health and disease effects of PPA by measuring mitochondrial function in ASD and age- and gender-matched control lymphoblastoid cell lines (LCLs) following incubation with PPA at several concentrations and durations both with and without an in vitro increase in reactive oxygen species (ROS). Mitochondrial function was optimally increased at particular exposure durations and concentrations of PPA with ASD LCLs, demonstrating a greater enhancement. In contrast, increasing ROS negated the positive PPA effect with the ASD LCLs, showing a greater detriment. These data demonstrate that enteric microbiome metabolites such as PPA can have both beneficial and toxic effects on mitochondrial function, depending on concentration, exposure duration and microenvironment redox state with these effects amplified in LCLs derived from individuals with ASD. As PPA, as well as enteric bacteria, which produce PPA, have been implicated in a wide variety of diseases, including ASD, diabetes, obesity and inflammatory diseases, insight into this metabolic modulator from the host microbiome may have wide applications for both health and disease.

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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”

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Authors
Frye, R. E., Rose, S., Chacko, J., Wynne, R., Bennuri, S. C., Slattery, J. C., Tippett, M., Delhey, L., Melnyk, S., Kahler, S. G., & MacFabe, D. F.
Affiliations
  • Arkansas Children's Research Institute (US)
  • University of Arkansas for Medical Sciences (US)
  • Western University (CA)
Corresponding author
Frye, R E
Venue
Translational Psychiatry
Published
2016-10-25
Volume
6
Issue
10
Pages
e927-e927
ISSN
2158-3188 (ISSN-L)
OpenAlex
W2532458527
Cited by
130
References
103
Citations by year
2026: 4 · 2025: 9 · 2024: 10 · 2023: 7 · 2022: 29 · 2021: 12 · 2020: 19 · 2019: 17 · 2018: 15 · 2017: 7
FWCI
6.75
Type
journal article
Language
en
Open access
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Autism Research Institute
  • Arkansas Biosciences Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
propionic acid, short-chain fatty acids, gut microbiota metabolites, mitochondrial function, autism spectrum disorder, lymphoblastoid cell lines, reactive oxygen species, propionic acidemia, redox state, host-microbiome interactions
MeSH terms
Autism Spectrum Disorder, Gastrointestinal Microbiome, Cell Line, Child, Humans, Male, Mitochondria, Propionates, Case-Control Studies, Mitochondrial Diseases, Propionic Acidemia

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