Gut bacterial characteristics in children with autism spectrum disorder according to symptom severity: a...

Autism spectrum disorder (ASD) is associated with alterations in gut microbiota. The gut-brain axis, which involves bidirectional communication between the gastrointestinal tract and the central nervous system, has been implicated in the pathophysiology of ASD. This study aimed to investigate the relationship between gut microbiota characteristics and symptom severity in children with ASD.

This cross-sectional study enrolled a total of 81 children with ASD aged 3-12 years, who were divided into mild-to-moderate (n = 35) and severe (n = 46) groups based on Childhood Autism Rating Scale scores. Fecal samples were collected for 16 S rRNA gene sequencing. Alpha diversity, beta diversity, and species composition were analyzed using R software. Linear Discriminant Analysis Effect Size (LEfSe) with a threshold of LDA score ≥ 2.0 and P < 0.05 was used to identify differentially abundant taxa.

The severe ASD group showed significantly lower Shannon index [4.04 (3.74-4.33) vs. 3.82 (3.40-4.23); P = 0.047] and Simpson index [0.95 (0.93-0.96) vs. 0.92 (0.90-0.96); P = 0.012] compared with the mild-to-moderate ASD group. Beta diversity analysis revealed significant separation between groups (PERMANOVA, R² = 0.048, P = 0.003). At the phylum level, the severe ASD group showed decreased Firmicutes (56.92%→47.46%) and increased Proteobacteria (5.92%→14.46%). At the family level, Enterobacteriaceae was increased (4.64%→13.08%), while Selenomonadaceae (2.64%→0.80%), Veillonellaceae (3.99%→2.70%), and Coriobacteriaceae (3.90%→2.36%) were decreased. At the genus level, Klebsiella showed a 2.8-fold increase (1.81%→5.06%), while Faecalibacterium (14.81%→11.84%) and Dialister (2.85%→1.95%) were decreased. LEfSe identified 11 differentially abundant taxa (LDA score ≥ 2.0, P < 0.05), with 10 taxa enriched in the mild-to-moderate ASD group, including Firmicutes (LDA = 4.69, P = 0.003), Coriobacteriia (LDA = 3.95, P = 0.026), Coriobacteriales (LDA = 3.95, P = 0.026), Bacteroides ovatus (LDA = 3.10, P = 0.048), and Sutterella (LDA = 2.65, P = 0.030), and several uncultured taxa. Only Fusobacteriaceae (family) was enriched in the severe ASD group (LDA = 3.40, P = 0.043).

Gut bacterial dysbiosis in ASD children is characterized by reduced diversity and altered composition, with more pronounced abnormalities in the severe ASD group. However, this study only evaluated bacterial communities (not fungi or viruses), and the cross-sectional design does not support causal inferences. These findings suggest that microbiota modulation may represent a potential therapeutic approach for ASD, though causal relationships remain to be established in longitudinal studies.