title: Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines.
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.
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: R E
authors: RE
authors: Frye
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: S
authors: S
authors: Rose
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: J
authors: J
authors: Chacko
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: R
authors: R
authors: Wynne
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: S C
authors: SC
authors: Bennuri
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: J C
authors: JC
authors: Slattery
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: M
authors: M
authors: Tippett
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: L
authors: L
authors: Delhey
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: S
authors: S
authors: Melnyk
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Arkansas Children's Research Institute, Little Rock, AR, USA.
authors: S G
authors: SG
authors: Kahler
authors: Kilee Patchell-Evans Autism Research Group, Division of Developmental Disabilities, Department of Psychology/Psychiatry, University of Western Ontario, London, ON, Canada.
authors: D F
authors: DF
authors: MacFabe
mesh_terms: D000067877:Autism Spectrum Disorder / Q000503:physiopathology*; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000503:physiopathology*; D011422:Propionates / Q000378:metabolism*; D056693:Propionic Acidemia / Q000503:physiopathology*
chemical_list: D011422:Propionates; C029658:propionic acid