Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection

Abstract

In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7–14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction (qPCR) assays were conducted on selected taxa implicated in ASD, including Sutterella spp., Bacteroidetes spp. and Prevotella spp. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S rRNA genes from fecal DNA was performed to an average depth of 208,000 and 107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of 44 NT siblings met ROME III criteria for at least one FGID. Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of 44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher (58–62 vs. 44, P < 0.0001) when compared to NT children without FGID. There was no significant difference in macronutrient intake between ASD and NT siblings. There was no significant difference in ASD severity scores between ASD children with and without FGID. No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings. Exploratory analysis of the 16S rRNA sequencing data, however, identified several low abundance taxa binned at the genus level that were associated with ASD and/or first order ASD*FGID interactions (FDR <0.1).

Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives

“…Nonetheless, even when genome-sequencing methods were comparable, opposing microbiota profiles of the three major phyla (Firmicutes, Bacteroidetes, and Proteobacteria) were found in patients with ASD as compared to controls [58,59], or no difference was found at all [60]. Finegold et al [59] observed increased ratios of Bacteroidetes and Proteobacteria, but decreased ratios of Firmicutes in ASD patients, while Williams et al [58] also found increased ratios of Proteobacteria, they observed increased ratios of Firmicutes and decreased ratios of Bacteroidetes as opposed to Finegold et al [59].…”

Consumption of a Bifidobacterium bifidum Strain for 4 Weeks Modulates Dominant Intestinal Bacterial Taxa and Fecal Butyrate in Healthy Adults

“…However, a subsequent study involving a larger population of autistic children reported the opposite result (i.e., a significant increase in Prevotella spp. [65]). In conclusion, the scientific literature is far from a final and unambiguous understanding of the role of a specific taxon in host health; plausibly, the same bacterial taxa of the gut microbiota may exert opposite effects on the host (health preserving versus health threatening), depending on physiological background.…”

Mucosal Prevalence and Interactions with the Epithelium Indicate Commensalism of Sutterella spp.

“…The abundance varied between 2 and 7% of total bacteria in the ileum and cecum. However, in another study no significant difference in the microbial composition, including the abundance of Sutterella , was observed between the autistic pediatric subjects with or without functional GI disorders compared to their siblings (Son et al, 2015). Thus, the results concerning the association of Sutterella spp.…”