Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder

Jul 27, 2021Gut

Underdeveloped gut bacteria as non-invasive markers to predict autism in children

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Abstract

Children with autism spectrum disorder (ASD) exhibited significant alterations in gut microbiome composition, characterized by increased bacterial richness (p=0.021).

ASD and chronological age significantly impacted the faecal microbiome of children.
Children with ASD showed altered gut microbiome composition compared to typically developing (TD) children (p<0.05).
Five bacterial species were identified as potential markers to distinguish ASD from TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery and validation cohorts, respectively.
Multiple pathways related to neurotransmitter biosynthesis were found to be depleted in the gut microbiome of children with ASD (p<0.05).
The dynamic development of growth-associated gut bacteria observed in TD children was absent in children with ASD across early life.

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OBJECTIVE: The gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD.

DESIGN: We performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model.

RESULTS: ASD and chronological age had the most significant and largest impacts on children's faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum.

CONCLUSIONS: Gut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.

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Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder

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