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Original research
Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder
  1. Yating Wan1,2,3,4,5,
  2. Tao Zuo1,2,3,4,
  3. Zhilu Xu1,2,3,4,5,
  4. Fen Zhang1,2,3,4,5,
  5. Hui Zhan1,2,3,4,5,
  6. Dorothy CHAN6,
  7. Ting-Fan Leung6,
  8. Yun Kit Yeoh1,5,7,
  9. Francis K L Chan1,2,3,4,5,
  10. Ruth Chan8,
  11. Siew C Ng1,2,3,4,5
  1. 1 Centre for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
  2. 2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
  3. 3 Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
  4. 4 Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
  5. 5 Microbiota I-Center (MagIC), Hong Kong, China
  6. 6 Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, China
  7. 7 Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China
  8. 8 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
  1. Correspondence to Professor Siew C Ng, Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong; siewchienng{at}cuhk.edu.hk; Dr Ruth Chan, Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China; ruth.chansm{at}gmail.com

Abstract

Objective The gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD.

Design We performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model.

Results ASD and chronological age had the most significant and largest impacts on children’s faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum.

Conclusions Gut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.

  • intestinal microbiology

Data availability statement

Data are available in a public, open access repository. (Raw sequence) data that support the findings of this study have been deposited in (NCBI) with the (PRJNA686821) accession codes [https://dataview.ncbi.nlm.nih.gov/object/PRJNA686821]

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Data availability statement

Data are available in a public, open access repository. (Raw sequence) data that support the findings of this study have been deposited in (NCBI) with the (PRJNA686821) accession codes [https://dataview.ncbi.nlm.nih.gov/object/PRJNA686821]

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Footnotes

  • Contributors Author contribution: YW conducted the study, performed DNA extraction, data analysis and drafted the manuscript. RC was responsible for ethical application, subject recruitment, collection of all questionnaire data and clinical samples, and commented on the manuscript. TZ, ZX, FZ, HZ, YKY and FKLC provided significant intellectual contribution to the manuscript. DFC and T-FL provided support and clinical advice on subject recruitment and DNA extraction. SCN designed the study, supervised the study and revised the manuscript.

  • Funding This work was supported by InnoHK, The Government of Hong Kong, Special Administrative Region of the People’s Republic of China. The work was also funded by a grant from the Health and Medical Research Fund (HMRF, grant number:14152251), Food and Health Bureau, Hong Kong SAR Government.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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