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Characteristics and functions of the gut microbiome in monozygotic twins with autism spectrum disorders of varying severity

Year: 2026

Type: article

Abstract: BACKGROUND Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by pronounced behavioral heterogeneity and individual variability. Growing evidence indicates a strong association between gut microbiota and ASD; however, differences in microbial functions across varying levels of ASD severity remain poorly understood. Monozygotic twins (MZs) provide an appropriate model for examining the influence of nonshared environmental factors in ASD. AIM To investigate the effects of the gut microbiome in MZs with ASD using 16S ribosomal RNA sequencing. METHODS Participants were recruited from the Chinese MZs with autism spectrum disorder (MZCo-ASD) cohort and stratified into mild MZCo-ASD and severe MZCo-ASD (MZCo-ASD-H) groups based on their Childhood Autism Rating Scale scores. Fecal samples were collected and analyzed using 16S ribosomal RNA sequencing. RESULTS Although overall microbial diversity did not differ significantly between the groups, gut microbiota composition was notably altered. At the genus level, Por phyromonas was significantly enriched in the MZCo-ASD-H group. Clusters of Orthologous Groups analysis revealed decreased expression of key genes in the MZCo-ASD-H group, including fructose-1,6-bisphosphatase, membrane-bound lytic murein transglycosylase, PasI (part of the RatAB toxin-antitoxin system), HmoA, and a glycoside hydrolase family 25 domain-containing protein. Kyoto Encyclopedia of Genes and Genomes Orthology analysis showed that msmF (K10118) and msmG (K10119), involved in oligosaccharide transport, were significantly downregulated in the MZCo-ASD-H group, suggesting a reduced microbial capacity for prebiotic carbohydrate utilization. CONCLUSION Despite similar overall diversity, children with severe ASD exhibited distinct gut microbiota structures and functional impairments. The enrichment of Porphyromonas , along with the reduced expression of genes involved in carbohydrate metabolism and stress responses in the high-severity group, suggests an association between gut microbial dysregulation and ASD severity. These findings provide new insights into microbiota-related mechanisms underlying ASD and highlight potential functional targets for intervention.

Source: World Journal of Psychiatry

DOI: 10.5498/wjp.v16.i2.111012

Authors: Yi-Yang Huang, Chun-Yan Li, Yun Li, Hui Fang, Xiao-Yan Ke