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Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines
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 disea...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290345/ https://www.ncbi.nlm.nih.gov/pubmed/27779624 http://dx.doi.org/10.1038/tp.2016.189 |
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author | 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 |
author_facet | 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 |
author_sort | Frye, R E |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5290345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52903452017-02-07 Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines 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 Transl Psychiatry Original Article 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. Nature Publishing Group 2016-10 2016-10-25 /pmc/articles/PMC5290345/ /pubmed/27779624 http://dx.doi.org/10.1038/tp.2016.189 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article 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 Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines |
title | Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines |
title_full | Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines |
title_fullStr | Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines |
title_full_unstemmed | Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines |
title_short | Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines |
title_sort | modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290345/ https://www.ncbi.nlm.nih.gov/pubmed/27779624 http://dx.doi.org/10.1038/tp.2016.189 |
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