Identification of Unique Gene Expression Profile in Children with Regressive Autism Spectrum Disorder (ASD) and Ileocolitis

Abstract

Gastrointestinal symptoms are common in children with autism spectrum disorder (ASD) and are often associated with mucosal inflammatory infiltrates of the small and large intestine. Although distinct histologic and immunohistochemical properties of this inflammatory infiltrate have been previously described in this ASDGI group, molecular characterization of these lesions has not been reported. In this study we utilize transcriptome profiling of gastrointestinal mucosal biopsy tissue from ASDGI children and three non-ASD control groups (Crohn's disease, ulcerative colitis, and histologically normal) in an effort to determine if there is a gene expression profile unique to the ASDGI group. Comparison of differentially expressed transcripts between the groups demonstrated that non-pathologic (normal) tissue segregated almost completely from inflamed tissue in all cases. Gene expression profiles in intestinal biopsy tissue from patients with Crohn's disease, ulcerative colitis, and ASDGI, while having significant overlap with each other, also showed distinctive features for each group. Taken together, these results demonstrate that ASDGI children have a gastrointestinal mucosal molecular profile that overlaps significantly with known inflammatory bowel disease (IBD), yet has distinctive features that further supports the presence of an ASD-associated IBD variant, or, alternatively, a prodromal phase of typical inflammatory bowel disease. Although we report qPCR confirmation of representative differentially expressed transcripts determined initially by microarray, these findings may be considered preliminary to the extent that they require further confirmation in a validation cohort.

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“…Though our study found that diarrhoea or constipation or both was common in 60% of the children with ASD, studies done lymphoid hyperplasia (NLH), enterocolitis, mucosal infiltration of immune cells in small and large intestine [12].…”

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“…They compared the metagenomic profile of ileal and colonic biopsies in children with ASD, ulcerative colitis (UC), and Crohn’s disease (CD). These investigators found that the transcriptome profiles of these tissues of children with ASD segregated apart from normal controls and alongside those with CD and UC when they used principal components analysis, as would be seen with an inflamed colon[19]. However, the authors did not identify why these tissues of ASD children had different transcriptional profiles; for example, they did not look for evidence of inflammation by assessing serum cytokines or fecal inflammatory markers such as calprotectin or interleukin-8.…”