Gut Microbial Alteration in Pediatric Autism Spectrum Disorder Based on 16S rRNA Sequence Analysis

Introduction: Emerging evidence highlights the critical role of gut microbes in the pathogenesis of autism spectrum disorder through interactions within the microbiota-gut-brain axis. Methods: This study conducted systematic bioinformatics analysis on 16S rRNA (V3-V4 region) sequencing data from 78 children with autism spectrum disorder and 68 neurotypical children from the NCBI database. Results: Microbial composition analysis revealed significant changes between patients with autism spectrum disorder and healthy controls across phylum-level and genus-level classifications. Elevated Bacteroidota/Firmicutes ratio was found in children with autism spectrum disorder compared to healthy controls. Microbial diversity analysis showed significant intergroup divergence: autism spectrum disorder subjects exhibited significantly elevated α-diversity, mainly reflected in the Chao1 index. Moreover, significant structural separation was observed between these two groups. LefSe analysis demonstrated distinct enrichment of Bacteroidota and Actinobacteriota at the phylum level, and Bacteroides, Prevotella, and Megamonas at the genus level in children with autism spectrum disorder. Conversely, control-associated enrichment of Firmicutes (phylum), along with genera Ruminococcus and Escherichia-Shigella, showed depletion in children with autism spectrum disorder. Functional prediction via PICRUSt2 demonstrated autism spectrum disorder-specific upregulation of cofactor and vitamin metabolism, contrasting with enrichment of terpenoid, polyketide, and xenobiotic degradation pathways in healthy controls. Discussion: These findings substantiate the microbiota-gut-brain axis hypothesis in the pathogenesis of autism spectrum disorder, revealing microbial composition and functional shifts potentially linked to nutritional compensation and inflammatory modulation. Conclusion: Gut microbial dysbiosis in autism spectrum disorder, characterized by altered microbial diversity and community structure, impairs xenobiotic metabolism, leading to neurotoxin accumulation that exacerbates core symptoms.