Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism

• DOI: 10.1038/s41398-017-0089-z
• Publication Date: 2018-02-01T11:16:01Z
• Authors: Shannon Rose; Sirish C. Bennuri; Jakeira E. Davis; Rebecca Wynne; John C. Slattery; Marie Tippett; Leanna Delhey; Stephan Melnyk; Stephen G. Kahler; Derrick F. MacFabe; Richard E. Frye
• Keywords: Male; 0303 health sciences; Mitochondrial Diseases; Autism Spectrum Disorder; Article; Cell Line; Gastrointestinal Microbiome; Mitochondria; Butyrates; Oxidative Stress; 03 medical and health sciences; Humans; Lymphocytes; Child; Reactive Oxygen Species

Butyrate (BT) is a ubiquitous short-chain fatty acid (SCFA) principally derived from the enteric microbiome. BT positively modulates mitochondrial function, including enhancing oxidative phosphorylation and beta-oxidation has been proposed as neuroprotectant. other SCFAs have also associated with autism spectrum disorders (ASD), condition dysfunction. We developed lymphoblastoid cell line (LCL) model of ASD, subset LCLs demonstrating dysfunction (AD-A) another normal function (AD-N). Given positive modulation on we hypothesized that would preferential effect AD-A LCLs. To this end, measured in ASD age-matched control (CNT) LCLs, all boys, following 24 48 h exposure to (0, 0.1, 0.5, 1 mM) both without an vitro increase reactive oxygen species (ROS). examined expression key genes involved cellular response stress. In CNT respiratory parameters linked adenosine triphosphate (ATP) production were attenuated by mM BT. contrast, significantly increased ATP but not AD-N context ROS exposure, for groups. was found modulate individual LCL respiration common set-point, set-point slightly higher compared The highest concentration (1 fission (PINK1, DRP1, FIS1) physiological stress (UCP2, mTOR, HIF1α, PGC1α) well thought be cognition behavior (CREB1, CamKinase II). These data show microbiome-derived SCFA activity, dependent concentration, microenvironment redox state, underlying cell. general, these suggest can enhance and/or dysfunction, may important metabolite help rescue energy metabolism during disease states. Thus, insight into metabolic modulator wide applications health since implicated variety conditions ASD. However, future clinical studies humans are needed define practical implications findings.