Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder Original paper

What was studied?

This study investigated the altered gut microbial profile in ASD and its relationship to metabolic abnormalities in children with Autism Spectrum Disorder (ASD). Using 16S rRNA sequencing in a large cohort of 143 ASD and 143 typically developing (TD) children, as well as metagenomic and metabolomic profiling in a subset of constipated ASD (C-ASD) children, the authors examined how microbial diversity, taxonomic structure, metabolic pathways, and fecal metabolites differ between ASD and TD groups. Analyses across age groups (2–13 years) provided insights into delayed microbial maturation, while integrated metabolic data explored links between microbial dysbiosis and neurotransmitter-related biochemical pathways relevant to the gut–brain axis.

Who was studied?

The research included 143 clinically diagnosed children with ASD (ages 2–13; predominantly male) and 143 age- and sex-matched TD controls. Among the ASD cohort, 52 had chronic constipation and 5 had diarrhea. A subset of 30 C-ASD children and 30 matched TD controls underwent deeper metagenomic and metabolomic analyses to clarify how gastrointestinal symptoms modulate microbial and metabolic patterns unique to ASD. All participants avoided antibiotics, probiotics, and prebiotics for three months prior to sampling.

Most important findings

ASD children showed significantly altered microbial profiles, including reduced phylum-level richness, increased Firmicutes/Bacteroidetes ratios, and enrichment of Proteobacteria and Actinobacteria. Genera such as Escherichia-Shigella, Dialister, and Bifidobacterium were elevated, while Prevotella, Megamonas, Ruminococcus, and Bacteroides were consistently depleted. Notably, TD children demonstrated age-related increases in microbial diversity, whereas ASD children did not, indicating delayed or disrupted microbial maturation. Metagenomic sequencing in C-ASD children revealed markedly reduced species diversity, with broad depletion across Bacteroides, Prevotella, and Phascolarctobacterium species. Functional pathway disruptions spanned lipid, amino acid, glycan, nucleotide, and xenobiotic metabolism. Metabolomic profiling showed abnormalities in neurotransmitter-related pathways, including serotonin, dopamine, GABA, histidine, and glutamate metabolism. Compounds such as indole-3-carboxylic acid, pyroglutamic acid, N-carboxyethyl-GABA, hexanoic acid, and dopaquinone displayed altered abundance and correlated strongly with microbial shifts—especially reductions in Bacteroides and Prevotella species and increases in Ruminococcus lactaris. These metabolite signatures integrate strongly with microbial changes known to affect the gut-brain axis.

Key implications

The findings highlight a robust microbiome-metabolite signature in ASD, particularly shaped by reductions in Prevotella- and Bacteroides-associated metabolic functions. Disrupted microbial maturation and neurotransmitter-linked metabolic pathways provide mechanistic clues to ASD-related behaviors and gastrointestinal symptoms. These results support the potential of microbiome-based biomarkers for ASD risk assessment and therapeutic strategies targeting specific taxa involved in neurotransmitter metabolism.

Citation

Zhou D, Mao X, Liu Q, et al. Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder. Gut Microbes. 2020;11(5):1246-1267. doi:10.1080/19490976.2020.1747329