Christine Wilson

 Introduction: Autism Spectrum Disorders (ASD) are a group of complex neurobiological disorders that are characterized by social and communication impairment, and fixed, repetitive, and stereotyped patterns of behavior, interests, and activities1. There is a prominent subgroup of individuals with ASD that suffer from gastrointestinal dysfunction3. Many studies have concluded that individuals with ASD have a different gut microbiome profile than neurotypic individuals, having shown markedly increased levels of Clostridia, Desulfovibrio, and Bacteroidetes4. It has been speculated that abnormalities in the microbiota and their metabolites could cause pathology via the gut-brain axis4. The bacteria elevated in individuals with ASD are known to produce propionic acid (PPA) as a metabolite, and PPA levels have been found to be excessively elevated in stool samples from individuals with ASD4,5. While PPA is a normal intermediate of mitochondrial metabolism, studies have suggested it plays a role in disorders involving mitochondrial dysfunction5,6. The question remains how PPA can serve as both a mitochondrial fuel and an agent of mitochondrial Methods: Article searches were conducted on PubMed primarily using search terms “autism spectrum disorder”, “gastrointestinal microbiome”, and “propionic acid”. Articles were excluded if published prior to 2012 or used small sample sizes. Results: A study measured mitochondrial respiratory parameters to determine whether the ability of mitochondria to utilize PPA was dependent on the PPA concentration, duration of exposure, microenvironment redox state, or the cell source. Lymphoblastoid cell lines (LCLs) of both control and ASD children were exposed to PPA. The results show that PPA increased mitochondrial respiratory parameters in both LCLs groups at a lower concentration and a shorter exposure time. At higher PPA concentrations, there was increased proton leak and increased ROS. When exposed to reactive oxygen species prior to PPA exposure, both LCLs showed an overall detrimental effect on the mitochondria’s ability to utilize PPA as a fuel source5,7. Conclusion: Research has demonstrated that PPA can affect a cell both positively and negatively depending on the concentration, duration of exposure, and redox state of the environment. This indicates that altered microbiome profiles and subsequent PPA levels in individuals with ASD can directly impact cell physiology through impacting mitochondrial function. Mitochondrial function disorders affect organs and systems that have the highest energy demand, which include the same organs and systems commonly affected in individuals with ASD7. This insight opens new avenues for ASD research and potential targets for treatments.

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4. Morris, G, Berk, M, Carvalho, A et The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease. Molecular Neurobiology. 2016.
5. Frye R, Rose S, Chacko J, et Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines. Translational Psychiatry. 2016;6(10):e927.
6. Thomas R, Meeking M, Mepham J, et The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders. Journal of Neuroinflammation. 2012;9:153.
7. Frye R, Rose S, Slattery J, MacFabe Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome. Microbial Ecology in Health and Disease. 2015;26:10.