Distinct diet-microbiome associations in autism spectrum disorder

Abstract Autism spectrum disorder (ASD) is linked to both altered gut microbiota and unhealthy diets; however, the mechanistic connections remain elusive. In this study, we conducted a systematic analysis of fecal microbiome metagenomic data, paired with granular dietary assessments and phenotypic profiles, across a cohort of 818 children (462 with ASD, 356 without ASD; mean age = 8.4 years; 27.3% female). By integrating dietary indices, nutrient intake, and food additive exposures, we uncovered ASD-specific linkages to the microbiome. Poor dietary quality correlated with aggregated core autistic symptoms, gastrointestinal complications, and atypical eating behaviors. Notably, children with ASD exhibited a more pronounced diet-microbiome interaction network compared to neurotypical peers, suggesting heightened microbial sensitivity to nutritional inputs. Furthermore, synthetic emulsifiers—specifically polysorbate-80 and carrageenan—were associated with disrupted microbial connectivity in ASD, a phenomenon attenuated in neurotypical children. Our findings elucidate the mechanistic links between dietary factors—particularly synthetic food additives—and microbiome dysregulation in ASD, urging a re-evaluation of dietary guidelines for ASD populations and laying the groundwork for personalized nutritional strategies.