Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines
Open accessAbstract
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”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [70]
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The Effects of Postpartum Yak Metabolism on Reproductive System Recovery
Shu, S., Fu, C., Wang, G., & Peng, W. (2022) · Metabolites · doi:10.3390/metabo12111113 · Cited by 3 · see citing works
Is Metabolic Screening Necessary in Children with Autism Spectrum Disorder? A Mini Review
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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)
- PMC
- PMC5290345
- 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
- gold
- doi.org
- 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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