Huang YY, Li CY, Li Y, Fang H, Ke XY. Characteristics and functions of the gut microbiome in monozygotic twins with autism spectrum disorders of varying severity. World J Psychiatry 2026; 16(2): 111012 [DOI: 10.5498/wjp.v16.i2.111012]
Corresponding Author of This Article
Xiao-Yan Ke, PhD, Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, No. 264 Guangzhou Road, Gulou District, Nanjing 210000, Jiangsu Province, China. kexynj@126.com
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Psychology
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Observational Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Feb 19, 2026 (publication date) through Feb 2, 2026
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World Journal of Psychiatry
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2220-3206
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Huang YY, Li CY, Li Y, Fang H, Ke XY. Characteristics and functions of the gut microbiome in monozygotic twins with autism spectrum disorders of varying severity. World J Psychiatry 2026; 16(2): 111012 [DOI: 10.5498/wjp.v16.i2.111012]
World J Psychiatry. Feb 19, 2026; 16(2): 111012 Published online Feb 19, 2026. doi: 10.5498/wjp.v16.i2.111012
Characteristics and functions of the gut microbiome in monozygotic twins with autism spectrum disorders of varying severity
Yi-Yang Huang, Chun-Yan Li, Yun Li, Hui Fang, Xiao-Yan Ke
Yi-Yang Huang, Department of Child Mental Health, Children’s Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
Chun-Yan Li, Department of Clinical Psychology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, Jiangsu Province, China
Yun Li, Hui Fang, Xiao-Yan Ke, Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
Author contributions: Huang YY designed the research and wrote the first manuscript; Huang YY, Li CY, Li Y, Fang H, and Ke XY contributed to conceiving the research and analyzing data; Huang YY and Ke XY conducted the analysis and provided guidance for the research. All authors reviewed and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 8177050957.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Nanjing Brain Hospital, Affiliated with Nanjing Medical University (approval No. 2017-KY021).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Yan Ke, PhD, Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, No. 264 Guangzhou Road, Gulou District, Nanjing 210000, Jiangsu Province, China. kexynj@126.com
Received: August 1, 2025 Revised: September 12, 2025 Accepted: November 11, 2025 Published online: February 19, 2026 Processing time: 181 Days and 23.5 Hours
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, Porphyromonas 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.
Core Tip: Autism spectrum disorder (ASD) is a highly heritable and heterogeneous neurodevelopmental disorder. Diagnostic and treatment options remain limited. Researchers are increasingly investigating the relationship between gut dysbiosis and ASD. This study examined gut microbiota composition and functions in monozygotic twins with varying ASD severity levels. Enrichment of Porphyromonas and reduced expression of genes involved in carbohydrate metabolism and stress responses were observed, suggesting a correlation between gut microbial dysbiosis and ASD severity.
