Molecular Characterization of Gastrointestinal Microbiota in Children with Autism (both with and without gastrointestinal dysfunction) and Their Neurotypical Siblings

Background:  In addition to core behavioral symptoms of autism, reports of gastrointestinal dysfunctions such as constipation, diarrhoea, and abdominal bloating are common. These observations have stimulated investigation of abnormalities of intestinal microbiota in autistic patients. Disruption of normal neurodevelopment by bacterial products, including lipopolysaccharides, toxins and metabolites, has been theorized to contribute to autistic pathology. We note that not all autistic individuals suffer from GI dysfunction; only a sub-population is affected. Although numerous intestinal microbial abnormalities have been identified in autism, conflicting results have often been reported. The purpose of this study was to identify whether a difference exists between the resident GI microbiota in children with autism (with and without GI dysfunction) and their neurotypical siblings.

Objectives:  Generally, the GI microbiota is influenced by diet and environmental sources. Therefore, this study was designed to identify differences (and/or similarities) of the gut microbiota in children with autism (with and without GI dysfunction) and their neurotypical siblings who share a similar environment. 

Methods:  Faecal samples from children with autism (without GI dysfunction: n = 23; with GI dysfunction; n = 28), healthy sibling controls (n = 53) were studied by using the bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP) procedure.

Results:  Differences in bacterial composition between cases and controls were evaluated by UniFrac and analysis of similarity matrices. Overall, Firmicutes (70%), Bacteroidetes (20%) and Proteobacteria (4%) were the most dominant phyla in the total sample. Although autism samples differed from control across several species-specific variables, there were no clinically meaningful significant differences between the groups. Nevertheless, when the autism group was divided according to GI dysfunction, several significant microbial differences were apparent, although, these were not consistent across individuals and showed substantial variation. 

Conclusions:  The data do not support an association between autism and gastrointestinal microbiota generally; however, the data do indicate that there is a sub-population within autism that experience GI dysfunctions which may be associated with aberrant GI microbiota. This study has implications for treatment strategies in autism aimed at manipulation of the microbiota to reduce GI dysfunction. Further research is required to determine the optimal approach (e.g. anti/pro-biotic, dietary) and such approaches may necessarily need to be tailored to individual patients based on clinical microbial findings. Other explanations for the gastrointestinal dysfunction in this population should be considered including elevated anxiety and self-restricted diets.