A comparison between children and adolescents with autism spectrum disorders and healthy controls in biomedical factors, trace elements, and microbiota biomarkers: a meta-analysis

Ping Lin; Qianwen Zhang; Junyu Sun; Qingtian Li; Dan Li; Mengyuan Zhu; Xiaomei Fu; Ling Zhao; Mengxia Wang; Xiaoyan Lou; Qing Chen; Kangyi Liang; Yuxin Zhu; Caiwei Qu; Zhenhua Li; Peijun Ma; Renyu Wang; Huafen Liu; Ke Dong; Xiaokui Guo; Xunjia Cheng; Yang Sun; Jing Sun

doi:10.3389/fpsyt.2023.1318637

A comparison between children and adolescents with autism spectrum disorders and healthy controls in biomedical factors, trace elements, and microbiota biomarkers: a meta-analysis

Front Psychiatry. 2024 Jan 9:14:1318637. doi: 10.3389/fpsyt.2023.1318637. eCollection 2023.

Authors

Ping Lin^#^{1

2}, Qianwen Zhang^#^{3

4}, Junyu Sun^#⁵, Qingtian Li⁶, Dan Li², Mengyuan Zhu², Xiaomei Fu², Ling Zhao², Mengxia Wang², Xiaoyan Lou², Qing Chen², Kangyi Liang², Yuxin Zhu², Caiwei Qu², Zhenhua Li², Peijun Ma², Renyu Wang², Huafen Liu^{3

4}, Ke Dong⁷, Xiaokui Guo⁷, Xunjia Cheng¹, Yang Sun⁸, Jing Sun^{9

10}

Affiliations

¹ Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
² Department of Clinical Laboratory, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, China.
⁴ Hangzhou Calibra Diagnostics, Hangzhou, China.
⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁶ College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Institute for Global Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁸ Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, China.
⁹ School of Medicine and Dentistry, Institute for Integrated Intelligence and Systems, Griffith University, Gold Coast Campus, Gold Coast, QLD, Australia.
¹⁰ Charles Sturt University, Orange, NSW, Australia.

^# Contributed equally.

Abstract

Introduction: Autism spectrum disorder (ASD) is a multifaceted developmental condition that commonly appears during early childhood. The etiology of ASD remains multifactorial and not yet fully understood. The identification of biomarkers may provide insights into the underlying mechanisms and pathophysiology of the disorder. The present study aimed to explore the causes of ASD by investigating the key biomedical markers, trace elements, and microbiota factors between children with autism spectrum disorder (ASD) and control subjects.

Methods: Medline, PubMed, ProQuest, EMBASE, Cochrane Library, PsycINFO, Web of Science, and EMBSCO databases have been searched for publications from 2012 to 2023 with no language restrictions using the population, intervention, control, and outcome (PICO) approach. Keywords including "autism spectrum disorder," "oxytocin," "GABA," "Serotonin," "CRP," "IL-6," "Fe," "Zn," "Cu," and "gut microbiota" were used for the search. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the article quality, and a random model was used to assess the mean difference and standardized difference between ASD and the control group in all biomedical markers, trace elements, and microbiota factors.

Results: From 76,217 records, 43 studies met the inclusion and exclusion criteria and were included in this meta-analysis. The pooled analyses showed that children with ASD had significantly lower levels of oxytocin (mean differences, MD = -45.691, 95% confidence interval, CI: -61.667, -29.717), iron (MD = -3.203, 95% CI: -4.891, -1.514), and zinc (MD = -6.707, 95% CI: -12.691, -0.722), lower relative abundance of Bifidobacterium (MD = -1.321, 95% CI: -2.403, -0.238) and Parabacteroides (MD = -0.081, 95% CI: -0.148, -0.013), higher levels of c-reactive protein, CRP (MD = 0.401, 95% CI: 0.036, 0.772), and GABA (MD = 0.115, 95% CI: 0.045, 0.186), and higher relative abundance of Bacteroides (MD = 1.386, 95% CI: 0.717, 2.055) and Clostridium (MD = 0.281, 95% CI: 0.035, 0.526) when compared with controls. The results of the overall analyses were stable after performing the sensitivity analyses. Additionally, no substantial publication bias was observed among the studies.

Interpretation: Children with ASD have significantly higher levels of CRP and GABA, lower levels of oxytocin, iron, and zinc, lower relative abundance of Bifidobacterium and Parabacteroides, and higher relative abundance of Faecalibacterium, Bacteroides, and Clostridium when compared with controls. These results suggest that these indicators may be a potential biomarker panel for the diagnosis or determining therapeutic targets of ASD. Furthermore, large, sample-based, and randomized controlled trials are needed to confirm these results.

Keywords: autism spectrum disorder; biomarkers; biomedical; microbiota; trace elements.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study is supported by the China Public Health Alliance Batch 1 Research Project (GWLM202014); the Shanghai Mental Health Center Project (2017-YJ-14 and 2021-YJ-10); and the Shanghai Natural Science Fund Project under grant 20ZR1447700.