Gut bacteria in children with autism spectrum disorders: challenges and promise of studying how a complex community influences a complex disease

Abstract

Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut-brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut-brain interactions could also be a direct result of microbially produced metabolites.

Keywords: GI problems; Prevotella; autism; gut microbiome; gut microflora; gut–brain interaction; meta-analysis; next-generation sequencing.

Fig. 1

Four most differentially abundant genera when children with ASD and neurotypical children are compared (blue box: neurotypical children; red box: children with ASD). (Figure from Kang et al. (21) under an open access license of PLoS journals called the Creative Commons Attribution (CC-BY) license.)

Fig. 2

Schematic of relationships among pairs at the 97% OTU level. Each grey or yellow circle represents an individual OTU, and paired OTUs are connected by a line if there is a high positive correlation (Pearson's R>0.8) among neurotypical samples. When paired OTUs were also present from autistic samples, lines connecting each OTU pair are highlighted either in blue or red depending on their correlation among autistic samples (either positive or negative correlation, respectively). If at least one OTU in the pair was absent from autistic samples, the connecting line is colored in green to show the changes in microbial interactions that resulted from the absence of the OTUs in children with ASD. Prevotella copri-like OTUs are highlighted in yellow to demonstrate how often their abundance is associated with the other in the network. (Figure from Kang et al. (17) under an open access license of PLoS journals called the Creative Commons Attribution (CC-BY) license.)

Fig. 3

The fecal microbiota of individuals with ASD in the U.S. shows a greater divergence from individuals in agrarian cultures compared to neurotypical controls. Unweighted UniFrac PCoA plot comparing data from children with ASD and neurotypical control in the U.S. (21) with a global survey of fecal microbial community composition conducted in individuals from Malawi, the Amazonas State of Venezuela, and the U.S. (35) (global gut). (a) Points colored by country of residence. (b) Same plot, but with points colored by study/ASD status.