Gut Microbiome Associations with Cingulate Cortex Structure and Autistic Symptom Severity

Recent research suggests a potential connection between the gut microbiota and autistic symptoms through the gut–brain axis. Neuroimaging studies have demonstrated that individuals with ASD exhibit abnormal structural variations in the cingulate cortex, a region essential to social cognition and emotional regulation. However, it remains unclear whether microbial composition influences brain structure. This study examined microbial diversity, differential abundance, and associations among microbiota, brain structure, and autistic symptoms. A total of 231 participants aged 4–18 were included, comprising 139 individuals with autism spectrum disorder (ASD) and 92 typically developing controls matched for age and sex. Gut microbiota profiles were analyzed using full-length 16S rRNA sequencing, and structural MRI was employed to quantify cortical thickness and surface area in the cingulate cortex. No significant differences were observed in alpha diversity indices; however, beta diversity differed significantly (p < 0.001). LEfSe analysis revealed distinct microbial compositions in ASD. Enterococcus abundance was associated with reduced cingulate cortical thickness and greater left isthmus surface area, whereas the association between Enterococcus and symptom severity was suggestive but inconclusive. These findings suggest that Enterococcus may be involved in microbiota–cingulate–behavior associations, providing insight into gut–brain mechanisms in ASD.