Gut microbiota are linked to gastrointestinal symptoms and behavioral changes but not inflammation in autism spectrum disorder: a cross-sectional analysis

BACKGROUND: Gastrointestinal (GI) symptoms are increased in children with autism spectrum disorder (ASD). We examined the relationship between ASD severity, intestinal inflammation, gut permeability, and dysbiosis. METHODS: Our cross-sectional study examined baseline data from a clinical trial and included stools from typically developing (TD) controls and siblings. GI symptom severity was assessed using GI severity index (GSI) with Bristol stool scoring, while ASD symptoms were quantified using Social Responsiveness Scale (SRS-2). Biomarkers including plasma zonulin, occludin, and S100A9, and fecal calprotectin levels, were measured to assess intestinal permeability and inflammation. Fecal microbiota was analyzed using 16S rRNA sequencing. RESULTS: Seventy-two children with ASD were included for biomarker analysis, and 135 children's stools for microbiome analysis. A statistically significant correlation was observed between GSI and SRS-2 scores (p = 0.02). GSI and SRS-2 scores did not correlate with measured biomarkers, none of which were elevated above published normal values. Children with ASD had reduced fecal richness and distinct clustering of organisms, with increased relative abundance of Fusicatenibacter, Blautia, Sarcina, and Eubacterium, compared to TD children. CONCLUSIONS: Children with ASD who had GI symptoms had increased Bacteroides and Ruminococci. Dysbiosis correlated with common GI symptoms, including flatulence, foul stools, and nighttime awakening. IMPACT: Children with ASD who have more disturbed social awareness are prone to more severe GI symptoms, reduced fecal microbial diversity and abnormal fecal microbial composition. Certain stool microbial taxa correlated with total GI symptom scores as well as with specific GI symptoms including flatulence, abdominal pain/irritability, and foul-smelling stools. However, we found no evidence of gastrointestinal or systemic inflammation, nor of increased gut permeability to explain the symptoms.