Multikingdom and functional gut microbiota markers for autism spectrum disorder

Area of Science:

• Microbiome research
• Neurodevelopmental disorders
• Metagenomics

Background:

• Previous studies on autism spectrum disorder (ASD) primarily focused on gut bacteria.
• The role of archaea, fungi, viruses, and overall gut microbiome function in ASD remains largely unexplored.

Purpose of the Study:

• To investigate alterations in the gut microbiome, including archaea, fungi, viruses, and functional pathways, in children with ASD.
• To assess the diagnostic potential of gut microbiota markers for ASD.

Main Methods:

• Metagenomic sequencing of fecal samples from 1,627 children (aged 1-13 years) with or without ASD.
• Integrated analyses of archaea, bacteria, fungi, viruses, microbial genes, and metabolic pathways.
• Machine learning models were developed to differentiate between children with and without ASD.

Main Results:

• Significant alterations were observed in 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 metabolic pathways in children with ASD.
• Single-kingdom panels achieved an area under the curve (AUC) of 0.68–0.87 for ASD differentiation.
• A multikingdom and functional marker panel demonstrated superior diagnostic accuracy (AUC 0.91), driven by ubiquinol-7 and thiamine diphosphate biosynthesis pathways.

Conclusions:

• The gut microbiome, encompassing multiple kingdoms and functional pathways, shows significant alterations in children with ASD.
• Multikingdom and functional gut microbiota markers hold promise as non-invasive diagnostic tools for ASD.
• These findings expand our understanding beyond bacterial associations in the ASD gut microbiome.