Dysbiosis in Autism
The defining characteristics of autism spectrum disorders (ASD) are impairments in cognition and social function. However, gastrointestinal (GI) symptoms have also been observed to be present in many individuals with ASD and the presence of those symptoms has been correlated with autism severity. Indeed, dietary modification and treatment with vancomycin have been reported to improve the social and cognitive function of autistic children. A recent study by Dr. Brent Williams and colleagues, published in the online journal PLoS One, goes one step further by examining the deficiencies in intestinal gene expression and microbial dysbiosis that underlie the presence of GI problems in children with autism.
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In the study, the research team took ileal and cecal biopsies from 15 children with autism and GI problems and 7 children suffering only from GI problems (control group). All the children were male and aged between 3 and 5 years of age. Human DNA and mRNA was extracted from the biopsies and used to identify the expression levels of various genes involved in carbohydrate digestion and transport. Bacterial 16S rRNA was extracted in order to identify the composition of the bacterial community present in the children’s intestines. The GI problems experienced in the two groups of children were similar with the majority suffering from food allergies including milk-related and/or wheat-related allergies. The GI symptoms were also similar in both groups and included diarrhea and changes in stool frequency and consistency.
Despite the similarities in GI problems between the two groups of children, gene expression analysis indicated that, compared to the control group, 14 out of the 15 autistic children had deficiencies in expression of at least 1 or more of the 5 disaccharidase and hexose transporter genes involved in carbohydrate digestion and transport. The expression of the genes in question is regulated by caudal homeobox 2 (CDX2) and deficiencies in expression of CDX2 were also observed in the autistic children. Changes in carbohydrate digestion and absorption due to deficiencies in gene expression are likely to influence the composition of the gut microbiome. Indeed, 16S rRNA sequencing indicated that although the overall microbiome diversity was similar between the two groups of children, the autistic children had significantly lower abundances of Bacteriodetes, increases in the ratio of Firmicutes to Bacteriodetes, and increases in Betaproteobacteria.
The causes and potential effects of these changes in gut function are difficult to identify but it is likely that the deficiencies in gene expression are likely to lead to maldigestion and malabsorption as well as microbial dysbiosis. There is also some evidence that in addition to causing GI problems, dysbiosis can have system-wide effects including alterations in immune responses and brain development and behavior. The identification of distinct changes that occur in autistic children with GI problems takes one step further towards understanding this multifaceted condition.
About the author: Ruth Warre is a freelance scientific writer and editor currently living in Toronto. She writes on a variety of subjects from microbiomes to neuroscience, in a variety of mediums from blogs to peer-reviewed articles.
Article:
Brent L. Williams, Mady Hornig, Timothy Buie, Margaret L. Bauman, Myunghee Cho Paik, Ivan Wick, Ashlee Bennett, Omar Jabado, David L. Hirschberg, and W. Ian Lipkin. (2011). Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with
Autism and Gastrointestinal Disturbances PLoS ONE 6(9): e24585.
DOI: 10.1371/journal.pone.0024585
