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Abstract

Autism Spectrum Disorder (ASD) is associated with alterations in the composition of the gut microbiota, which have been implicated in neurological manifestations via the gut–brain axis. Early-life exposure to antibiotics constitutes a key environmental factor shaping microbiota development; however, the resistome profile underlying ASD-associated dysbiosis remains insufficiently defined. In this metagenomic investigation, we assessed the abundance and diversity of antibiotic resistance genes (ARGs) in fecal samples obtained from four children with ASD and their four neurotypical siblings. High-throughput shotgun sequencing generated 10-15 Gb of data per sample. Resistome characterization was performed using the Comprehensive Antibiotic Resistance Database (CARD) and the BacMet database. The analysis revealed a pronounced enrichment of multi-class ARGs encompassing ten major antibiotic categories in ASD samples relative to controls. Notably, genes conferring resistance to tetracyclines and penams were increased by 2.06-fold and 6.86-fold, respectively, in ASD-associated microbiota. Mechanistic profiling indicated the presence of dual-pathway resistance architectures: tetracycline resistance was mediated by both efflux pump systems and ribosomal protection proteins, whereas penam resistance involved enzymatic inactivation by beta-lactamases in conjunction with antibiotic target modification via altered penicillin-binding proteins. Taxonomic profiling demonstrated a dysbiotic community structure in ASD, characterized by dominance of eight bacterial species accounting for 99% of the relative abundance. This assemblage included putative pathogenic taxa such as Escherichia coli D, Proteus terrae, and Klebsiella oxytoca, alongside a pronounced reduction in beneficial commensals, including Faecalibacterium prausnitzii and Bifidobacterium species. The observed mechanistic heterogeneity and multidrug resistance phenotypes in ASD-enriched taxa are consistent with cumulative antimicrobial selection pressure during critical developmental periods. In a nutshell, these data identify an elevated pediatric resistome as a defining feature of ASD-associated gut dysbiosis and highlight the imperative for targeted antimicrobial stewardship strategies in this vulnerable population.

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119

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140

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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