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

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

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 14 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1318637

DOI=10.3389/fpsyt.2023.1318637

ISSN=1664-0640

ABSTRACT=The etiology of ASD remains multifactorial and not yet fully understood. 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. Medline, PubMed, ProQuest, EMBASE, Cochrane Library, Psycinfo, Web of science, and EMBSCO have been searched for publications within 2012-2023 with no language restrictions using PICO approach. Key words including "autism spectrum disorder", "oxytocin", "GABA", "Serotonin", "CRP", "IL-6", "Fe", "Zn", "Cu", and "gut microbiota" were used for the search. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess the article quality and random model was used to assess the mean difference and standardized difference between ASD and control group in all biomedical markers, trace elements and microbiota factors. From 76,217 records, 43 studies met inclusion and exclusion criteria and 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. Children with ASD have significant 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 these indicators maybe potential biomarker panel for diagnosis or therapeutic targets of ASD. Further large sample based and randomized controlled trials are needed to confirm these results.