Randy Volkmer II

Introduction.  Autism Spectrum Disorder (ASD) is a multifactorial disease that displays varying degrees of behavioral, social, and/or intellectual incapacity in the individual that it affects¹.  Causes of ASD have been widely speculated, but recent discovery of differences in the intestinal microbiome of individuals with ASD and individuals without ASD has led to further investigation on the direct and indirect impacts of altered host bacterial flora and its role in ASD development^1-5.  Methods.  The microbiome of human stool samples were compared in children with ASD to children without ASD via PCR (Polymerase Chain Reaction) testing as well as Giemsa and Gram staining^2,3.  Mice with induced ASD syndromes were had their subsequent microbiomes tested against non-VPA exposed mice by gas chromatography⁴.  Microbiota Transfer Therapy (MTT) was conducted by transplanting intestinal microbiotas of healthy children subjects in children with ASD⁵.  The microbiomes in the children with ASD were then monitored for the remainder of the study by a DNA isolation kit, and the symptomology scores were based on the CARS system⁵.  Results.  Intestinal microbiomes in both mouse and human subjects with ASD were found to have increased levels of microbes such as Clostridia perfringens, Enterobacteriacea, Candida, and Erysipelothrichales^2-4.  There was also found to be a decrease in levels of Lactobacillus and Bacteriodales (Bacteriodetes Kingdom) in subjects with ASD as compared to their healthy counterparts^3,4.  Serotonin (5-HT) levels were decreased in the intestines of VPA exposed mice compared to non-VPA exposed mice in contrast to increased levels of Butyrate present in the VPA exposed mice⁴.  Fecal Transplantation resulted in decreased ASD symptomology as well as increased levels of Bacteriodetes and Bifidobacterium⁵.  Conclusion.  Altered bacterial varieties within the intestines directly affect the synthesis of metabolites such as serotonin and butyrate.  Serotonin is predominately produced in the intestinal tract and decreased levels of 5-HT are strongly correlated with differential changes in the GABA systems located in the limbic system of the brain, which is heavily involved with emotional learning and memory⁶.  Butyrate can cross the Blood-Brain Barrier and has been shown to inhibit enzymes in the CNS such as HDAC (histone deacetylase), which plays a role in maturation of oligodendrocytes in the hippocampus^4,7.  Either one of these metabolite alterations could be a factor in the development of ASD. The results of the MTT indicates its efficacy in both directly modifying and sustaining the levels of normal intestinal bacteria in subjects with ASD as well as alleviating some of the classic behavioral findings in patients with ASD.

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3. Iovene MR, Bombace F, Maresca R, et al. Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. Mycopathologia. 2017;182(3-4):349-363.
4. de Theije CG, Wopereis H, Ramadan M, et al. Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav Immun. 2014;37:197-206.
5. Kang DW, Adams JB, Gregory AC, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017;5(1):10.
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