Comparison of gut microbiota in autism spectrum disorders and neurotypical boys in China: A case-control study Original paper

What was studied?

This case-control study investigated the gut microbiome signature associated with autism spectrum disorder (ASD) in boys in China, aiming to identify microbial patterns that could support early-stage clinical recognition of ASD. The research compared fecal microbial composition between ASD and neurotypical boys, making “gut microbiome signature in Chinese boys with ASD” central to the study’s purpose. Using 16S rRNA sequencing and metagenomic profiling, the study examined alpha- and beta-diversity, taxonomic shifts from phylum to strain level, and machine-learning-based microbial classifiers. According to page 3 and the LEfSe plots shown on page 4, the study mapped specific genera and species whose abundances diverged sharply between groups. The analysis also assessed the predictive power of a Random Forest classifier, illustrated clearly in the ROC curve on page 5, to determine whether microbial taxa could distinguish ASD from typical development.

Who was studied?

The study included 71 boys aged 3–6 years with ASD and 18 age-matched neurotypical boys, the largest ASD gut-microbiome cohort reported in China to date. All participants were male to remove sex-based microbial variability. ASD diagnosis followed both the Autism Behavior Checklist and DSM-5 criteria. Both groups were comparable in age, though ABC scores differed substantially (ASD mean 79.82 vs. control mean 8.77). Children with neurological diseases, antibiotic/probiotic exposure in the prior month, or major gastrointestinal conditions were excluded. Fecal samples were collected using standardized kits and processed using validated sequencing pipelines.

Most important findings

The ASD group showed significantly higher microbial richness and alpha diversity, as demonstrated in the boxplots on page 3 (Shannon, Simpson, Observed Species). Beta-diversity PCoA plots revealed distinct community clustering between ASD and controls, indicating marked microbial shifts. At the phylum level, ASD microbiota showed increased Firmicutes, Proteobacteria, and Actinomycetes, with reduced Bacteroidetes, lowering the Bacteroidetes/Firmicutes ratio. LEfSe analysis showed that controls had higher levels of Escherichia, Shigella, Veillonella, Akkermansia, Dialister, Bifidobacterium, and Streptococcus, whereas ASD children exhibited elevated Eisenbergiella, Klebsiella, Faecalibacterium, and Blautia. Metagenomic analysis identified ten discriminatory strains—including Bifidobacterium longum, Streptococcus thermophilus, Clostridium ramosum, and Prevotella buccae—that formed a predictive model with an AUC of 0.947.

Key implications

The findings reinforce the concept of a gut–brain microbiome axis, highlighting microbial patterns uniquely associated with ASD. Reduced Bifidobacterium (a GABA-producing genus), lower Dialister, and increased Klebsiella may reflect disruptions in neuroactive metabolite availability, immune modulation, and gut barrier dynamics. The robust machine-learning classifier underscores the potential for microbiome-based biomarkers to support early ASD screening. However, causality remains unresolved, requiring longitudinal and interventional validation. Clinically, the results encourage deeper exploration of microbial contributors to neurodevelopment and justify continued evaluation of targeted microbiome modulation strategies.

Citation

Ye F, Gao X, Wang Z, Cao S, Liang G, He D, et al. Comparison of gut microbiota in autism spectrum disorders and neurotypical boys in China: A case-control study. Synthetic and Systems Biotechnology. 2021;6:120-126. doi:10.1016/j.synbio.2021.03.003