Gut microbial and clinical characteristics of individuals with autism spectrum disorder differ depending on the ecological structure of the gut microbiome

Understanding the relationship between the gut microbiome and autism spectrum disorder (ASD) is challenging due to the heterogeneous nature of ASD. Here, we analyzed the microbial and clinical characteristics of individuals with ASD using enterotypes. A total of 456 individuals participated in the study, including 249 participants with ASD, 106 typically developing siblings, and 101 controls. The alpha and beta diversities of the ASD, sibling, and control groups did not show significant differences. Analysis revealed a negative association between the Bifidobacterium longum group and the Childhood Autism Rating Scale, as well as a negative association between the Streptococcus salivarus group and the Social Responsiveness Scale (SRS) within the ASD group. When clustered based on microbial composition, participants with ASD exhibited two distinct enterotypes, E1 and E2. In the E2 group, the SRS score was significantly higher, and the Vineland Adaptive Behavior Scale score was significantly lower compared to the E1 group. Machine learning results indicated that the microbial species predicting SRS scores were distinct between the two enterotypes. Our study suggests that the microbial composition in individuals with ASD exhibits considerable variability, and the patterns of associations between the gut microbiome and clinical symptoms may vary depending on the enterotype.