Rachael Helpenstell Counts

 Introduction.  Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by limited social communication skills and stereotypical behavioral patterns.^1,2 Many ASD patients also have gastrointestinal (GI) symptoms.² Because of the heterogeneity of ASD, it is difficult to identify a single cause. However, environment, especially the intestinal microbiome, plays an important role.^1-3 The intestinal microbiome can be altered by events during childbirth,³ antibiotic usage,^1,2 and diet,^1,3 causing Gut-Brain Axis Dysfunction. Children with ASD have been shown to have microbiome dysbiosis when compared to neurotypical (NT) children.^2,4-10 Fecal Microbiota Transfer (FMT) can alter the microbiome,^1-4 and has been used in the past to treat irritable bowel syndrome, which has GI symptoms similar to those in ASD.^2,3 Studies have shown FMT using healthy donor stool to decrease ASD symptoms for at least 8 weeks following treatment.⁹ These findings could suggest a potential FMT treatment for long-term reduction in ASD symptoms.  Methods.  Experimental studies selected compare the intestinal microbiome composition in children with ASD versus age and sex-matched NT children. Microbiome composition from stool samples was analyzed via pyro-sequencing with the QIAamp DNA Stool Mini Kit^,5,7 or FastDNA SPIN Kit for Feces.⁶ Composition was statistically correlated with presence/absence of ASD, presence/severity of GI symptoms, and severity of behavioral symptoms.^5-6 A study comparing the intestinal microbiome composition before and after FMT was used. Microbiome composition after FMT was statistically correlated with presence of GI and behavioral symptoms.⁹   Results. Studies show ASD children to have a microbiome with altered expression of genes associated with increased intestinal permeability compared to NT children.^4,5 This includes decreased tight-junction proteins and increased pore-forming proteins⁴ and pro-inflammatory cytokines.^4,5,6 Studies show that compromise of blood brain barrier integrity can lead to increased access of bacterial toxins and pro-inflammatory cytokines to the central nervous system, contributing to neuroinflammation and ASD symptoms in predisposed individuals.^2,4,5,6 Further, the microbiome of ASD children was associated with decreased Bacteroidetes, increased Firmicutes, and decreased overall diversity when compared to NT children. ^5-10 FMT was associated with a shift in microbiota composition to levels of NT children, with associated improvement in GI and behavioral symptoms in ASD children.⁹   Conclusion.  Studies have found that ASD children have microbiota composition different from NT children, which contributes to the pathogenesis of ASD. Treatments, such as FMT, leading to increased composition of Bacteroidetes, decreased Firmicutes, and increased overall bacterial diversity could contribute to reduction in the behavioral and GI symptoms of ASD.

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2. Ding, HT, Taur, Y, Walkup JT. Gut microbiota and autism: Key concepts and findings.   Autism Dev Disord. 2017;47:480-489. https://link.springer.com/article/ 10.1007/s10803-016-2960-9. Accessed March 19, 2017.
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7. Kang, D., et al. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLOS ONE. 2013;8(7). http://journals.plos.org/ plosone/article?id=10.1371/journal.pone.0068322. Accessed April 20, 2017.
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9. Kang, D. et al. Microbiota transfer therapy alters gut ecosystem and improve gastrointestinal and autism symptoms: an open-label study. 2017;5(10). https://microbiomejournal-biomedcentral-com.lib-ezproxy.tamu.edu:9443/articles/10.1186/s40168-016-0225-7. Accessed February 21, 2017.
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