A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

Zhang，Mengxiang1; Chu，Yanan2; Meng，Qingren3; Ding，Rui1,4; Shi，Xing5; Wang，Zuqun1,4; He，Yi1,4; Zhang，Juan6; Liu，Jing7; Zhang，Jie8; Yu，Jun2; Kang，Yu2; Wang，Juan1

2020-10-21

10.1126/sciadv.aba3760

Science Advances   影响因子和分区

2375-2548

2375-2548

Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy-quasi-paired cohort-and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD.

SCI ; EI ; SSCI

英语

NI论文

其他

Grant of Peking University Health Science Center[BJMU88443Y0306][BMU2018MX002] ; National Science Foundation of China[31671350][31970568] ; National Science and Technology Major Project of China[2018ZX10712001-018-002] ; Programs of the Chinese Academy of Sciences[QYZDY-SSW-SMC017][Y8YZ02E001]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000582114600008

AMER ASSOC ADVANCEMENT SCIENCE

20204509462842

Mitochondria ; Enzymes ; Diagnosis

Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6

2-s2.0-85094098003

Scopus

1.Department of Biomedical Informatics,School of Basic Medical Sciences,Peking University,Beijing,100191,China
2.CAS Key Laboratory of Genome Sciences and Information,Beijing Institute of Genomics,Chinese Academy of Sciences,China National Center for Bioinformation,Beijing,100101,China
3.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
4.Autism Research Center,Peking University Health Science Center,Beijing,100191,China
5.Department of Respiratory and Critical Care Medicine,Peking University People's Hospital,Beijing,100044,China
6.Department of Pediatrics,Peking University Third Hospital,Beijing,100191,China
7.Key Laboratory of Mental Health,Ministry of Health,Peking University Institute of Mental Health,Peking University Sixth Hospital,Beijing,100191,China
8.Children Health Care Center,Xi'an Children's Hospital,Xi'an,710003,China

Zhang，Mengxiang,Chu，Yanan,Meng，Qingren,et al. A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children[J]. Science Advances,2020,6(43).

Zhang，Mengxiang.,Chu，Yanan.,Meng，Qingren.,Ding，Rui.,Shi，Xing.,...&Wang，Juan.(2020).A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children.Science Advances,6(43).

Zhang，Mengxiang,et al."A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children".Science Advances 6.43(2020).