Implications of Acyl-carnitine and Fatty Acid Oxidation Alterations by Intestinal Microbiome in Autism Spectrum Disorder

 Natasha Abdullah

Introduction: Autism Spectrum disorder (ASD) is a spectrum of developmental disabilities that is marked by social, communication, and behavior impairments. Both environmental and genetic factors have been implicated in the etiology of ASD. With a larger emphasis on intestinal microbiome in various disease pathologies and the efficacy of certain diets in ameliorating symptoms, certain subsets of ASD could have microbiome variation. Several studies have indicated that there is a significant change in the composition of the intestinal microbiome of certain subsets of ASD. Overlap in mutations of certain mitochondrial diseases demonstrate that the change in microbiomes of subsets of ASD, could affect the metabolism of short chain fatty acids (SCFAs). SCFAs can  inhibit acyl-carnitine, an enzyme necessary for the function of basic fatty oxidation pathways in mitochondria. Further research into overlap of mitochondrial dysfunction and ASD symptoms, as well as probiotic use for treatment of ASD is needed. Methods: Several studies I looked at established connection from the composition of the intestinal microbiomes, to potential use of probiotics and specific diets to ameliorate symptoms of ASD. Studies have examined the changes in intestinal flora from children, neurotypical siblings, and control populations. For instance, Finegold et al examined the fecal microbial flora of 33 subjects with various severities of autism with gastrointestinal symptoms, 7 siblings not showing autistic symptoms (sibling controls) and eight non-sibling control subjects, using the bacterial tag encoded FLX amplicon pyrosequencing procedure.  McFabe et al examined a rat model with PPA infusions via IVC for 1 minute to observe changes in behavioral patterns of the subjects. Results: Finegold et al found statistically significant differences when comparing autistic and control subjects. Phyla Bacteroidetes and Firmicutes showed the most difference between groups of varying severities of autism. Bacteroidetes is linked to elevated PPA levels.  Mcabe et al found  “PPA-infused rats showed bouts of increased repetitive locomotor activity, turning, retropulsion, tics, social impairment, perseveration, and restrictive preference for objects versus novel rats.”

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