Faecal Fermentation Products and Microbiota Are Altered in Children with Autism Spectrum Disorder

Background:

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition and recent studies have implicated gastrointestinal (GI) factors. Evidence is emerging that the profiles of the GI microbiota (Song et al. 2004; Finegold et al. 2010) and fermentation products (Yap et al. 2010) in individuals with ASD are different from those without ASD. Finegold et al. (2002) have reported a relationship between regressive autism and altered GI microbiota. Williams et al. (2012) found intestinal biopsy samples from more than half of children with ASD and GI disturbance (ASD-GI) were PCR positive for Sutterella compared with none of a control group (CON-GI). Further, the modulation of intestinal microbiota in children with ASD through the use of probiotics such as Lactobacillus plantarumWCSF1 has been shown to improve behaviour and bowel health outcomes (Parracho et al. 2010). Large bowel fermentation products, such as short chain fatty acids (SCFAs), phenols and ammonia, can have beneficial or detrimental effects on health and can contribute to various physiological and neurological processes. Studies conducted by MacFabe and colleagues in rats (2007; 2008) have shown that intraventricular administration of propionic acid induced behaviours resembling ASD and reproduced the neuropathological changes reported to occur in ASD.

Objectives:

1) To measure fermentation products in faeces of children with and without ASD to examine whether there is an underlying disturbance in fermentation processes in the disorder.

2) To measure relative abundances of various GI bacteria, including Clostridium species, members of the Bacteroides fragilis group, Akkermansia muciniphila, Prevotella species and Sutterella species, which are emerging as important markers of GI health.

Methods:

Faecal samples (48 h) were collected from children with autism (n=23, ASD), siblings (n=22, SIB) and community controls (n=9, CON). Faecal concentrations of carbohydrate and protein fermentation products, including SCFA, ammonia, phenol and p-cresol, were measured. Total faecal bacterial DNA was isolated and used for estimating numbers of selected bacterial species using quantitative real-time PCR

Results:

There were significant increases in faecal concentrations of total SCFAs and propionic acid in children with ASD compared to community controls. Moreover, a higher ammonia level appeared in children with ASD than siblings. In addition, lower relative abundances of Bifidobacteria species and the mucolytic bacterium Akkermansia muciniphila were shown in the faeces of children with ASD compared to controls (SIB and CON). Further, there was a higher faecal abundance of Sutterella species found in children with ASD compared with community controls.

Conclusions:

These findings indicate that gut microbiota and fermentation processes are altered in children with ASD. Since fermentation and microbial activity are influenced by diet, food selection and/or probiotic interventions may be important in managing ASD if such changes contribute to the phenotypic presentation of the disorder.