Abstract
Proliferation and/or depletion of clusters of specific bacteria regulate intestinal functions and may interfere with neuro-immune communication and behavior in patients with autism spectrum disorder (ASD). Consistently, qualitative and quantitative alteration of bacterial metabolites may functionally affect ASD pathophysiology. Up to date, age-restricted cohort studies, that may potentially help to identify specific microbial signatures in ASD, are lacking. We investigated the gut microbiota (GM) structure and fecal short chain fatty acids (SCFAs) levels in a cohort of young children (2–4 years of age) with ASD, with respect to age-matched neurotypical healthy controls. Strong increase of Bacteroidetes and Proteobacteria and decrease of Actinobacteria was observed in these patients. Among the 91 OTUs whose relative abundance was altered in ASD patients, we observed a striking depletion of Bifidobacterium longum, one of the dominant bacteria in infant GM and, conversely, an increase of Faecalibacterium prausnitzii, a late colonizer of healthy human gut and a major butyrate producer. High levels of F. prausnitzii were associated to increase of fecal butyrate levels within normal range, and over representation of KEGG functions related to butyrate production in ASD patients. Here we report unbalance of GM structure with a shift in colonization by gut beneficial bacterial species in ASD patients as off early childhood.
Highlights
Autism spectrum disorders (ASD) are a group of severe neurodevelopmental conditions characterized by stereotypic behavior with defective communication and social interaction deriving from a combination of genetic and environmental factors (Hallmayer et al, 2011)
High-throughput sequencing analysis of bacterial 16S rRNA V3–V4 regions was conducted on fecal samples of autism spectrum disorder (ASD) and healthy controls (HCs)
Bacterial diversity within communities was significantly higher in the ASD group than in the controls, as indicated by the Shannon index, while no significant differences in number of observed species were detected between the two groups (Table 2)
Summary
Autism spectrum disorders (ASD) are a group of severe neurodevelopmental conditions characterized by stereotypic behavior with defective communication and social interaction deriving from a combination of genetic and environmental factors (Hallmayer et al, 2011). Several human pre-clinical studies have described abnormal gut bacteria in children with ASD. Reduction of Bacteroidetes in ASD young subjects and, at genus level, increase of Collinsella, Corynebacterium, Dorea, and Lactobacillus together with significant reduction of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella have been reported (Strati et al, 2017). With previous studies, the ratio of Bacteroidetes/Firmicutes was significantly higher in Chinese children with ASD probably due to different living environment and eating habits (Zhang et al, 2018). Along with GM composition, SCFAs levels, which are modulated by functional gut microbes, showed changes both in human patients and mouse models of ASD, possibly contributing to ASD symptoms. Findings in animal models supported this hypothesis (MacFabe et al, 2007; de Theije et al, 2014)
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