Metabolomics mechanism of sulforaphane in the treatment of autism spectrum disorders
10.3760/cma.j.cn113661-20230921-00089
- VernacularTitle:萝卜硫素治疗孤独症谱系障碍的代谢组学机制研究
- Author:
Si DAI
1
;
Yanting HOU
;
Jingjing LIN
;
Yidong SHEN
;
Daomeng CHENG
;
Renrong WU
;
Jianjun OU
Author Information
1. 中南大学湘雅二医院精神科 国家精神疾病医学中心 国家精神心理疾病临床医学研究中心，长沙410011
- Publication Type:Journal Article
- Keywords:
Autistic disorder;
Metabolomics;
Biological markers;
Sulforaphane
- From:
Chinese Journal of Psychiatry
2024;57(6):337-344
- CountryChina
- Language:Chinese
-
Abstract:
Objective:The aim of this study was to explore the molecular mechanisms of sulforaphane in the treatment of autism spectrum disorders (ASD), identify metabolomic biomarkers associated with efficacy and construct efficacy prediction models.Methods:Forty children with ASD who were treated in Second Xiangya Hospital of Central South University and Guangzhou Huiai Hospital were recruited from August 2016 to May 2019. The patients were randomly allocated into sulforaphane treatment group ( n=26) and placebo group ( n=14). The OSU Autism Rating Scale-DSM-Ⅳ (OARS-4) was used to assess the change in clinical symptoms of children with ASD at baseline, week 4, week 8 and week 12 of treatment. A generalized linear mixed model was used to compare the differences in OARS-4 scale scores between groups and time. Plasma samples were collected from patients before and after treatment for untargeted metabolomic detection using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Differential metabolites were screened using ANOVA-component analysis, and metabolic pathway analysis was performed. Then, spearman correlation analysis was performed to find differential metabolites significantly associated with the efficacy of sulforaphane treatment, and finally Fisher′s discriminant analysis was used to screen for efficacy predictors. Result:After 12 weeks of treatment, the clinical symptoms improvement was significantly better in the sulforaphane group than in the placebo group ( F=14.11, P<0.001). There were differences in a total of 201 metabolites between the two groups, which were mainly significantly enriched in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Spearman′s correlation analysis showed that taurine, phosphatidylserine and lysophosphatidylserine were significantly positively associated with symptom changes in patients with ASD ( r=0.643, 0.401, 0.414, P<0.05 or 0.001), while lysophosphatidylethanolamine, sphingomyelin and triglyceride metabolites were significantly negatively associated with symptom changes ( r=-0.481--0.392, all P<0.05). Among them, sphingomyelin (d35∶1) and taurine entered the Fisher′s discriminant analysis model, which the accuracy of efficacy prediction was 84.6%(22/26). Conclusions:The molecular mechanism of sulforaphane in improving ASD related clinical symptoms may be related to cell membrane phospholipid metabolism. Sphingomyelin (d35∶1) and taurine may be possible predictors on the efficacy of sulforaphane in the treatment of ASD.
