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萝卜硫素在自闭症谱系障碍中的治疗效果及其与肠道微生物群的关联:动物模型和人类纵向研究。

Therapeutic efficacy of sulforaphane in autism spectrum disorders and its association with gut microbiota: animal model and human longitudinal studies.

作者信息

Yang Jiexian, He Li, Dai Si, Zheng Huihui, Cui Xilong, Ou Jianjun, Zhang Xiaojie

机构信息

Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

出版信息

Front Nutr. 2024 Jan 8;10:1294057. doi: 10.3389/fnut.2023.1294057. eCollection 2023.

DOI:10.3389/fnut.2023.1294057
PMID:38260076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10800504/
Abstract

INTRODUCTION

Sulforaphane (SFN) has been found to alleviate complications linked with several diseases by regulating gut microbiota (GM), while the effect of GM on SFN for autism spectrum disorders (ASD) has not been studied. Therefore, this study aimed to investigate the relationship between the effects of SFN on childhood ASD and GM through animal model and human studies.

METHODS

We evaluated the therapeutic effects of SFN on maternal immune activation (MIA) induced ASD-like rat model and pediatric autism patients using three-chamber social test and OSU Autism Rating Scale-DSM-IV (OARS-4), respectively, with parallel GM analysis using 16SrRNA sequencing.

RESULTS

SFN significantly improved the sniffing times of ASD-like rats in the three-chamber test. For human participants, the average verbal or non-verbal communication (OSU-CO) scores of SFN group had changed significantly at the 12-wk endpoint. SFN was safe and no serious side effects after taking. GM changes were similar for both ASD-like rats and ASD patients, such as consistent changes in order , family and genus . Although the gut microbiota composition was significantly altered in SFN-treated ASD-like rats, the alteration of GM was not evident in ASD patients after 12 weeks of SFN treatment. However, in the network analysis, we found 25 taxa correlated with rats' social behavior, 8 of which were associated with SFN treatment in ASD-like rats, For ASD patients, we found 35 GM abundance alterations correlated with improvements in ASD symptoms after SFN treatment. Moreover, family and genus were found to be associated with SFN administration in the network analyses in both ASD-like rats and ASD patients.

DISCUSSION

These findings suggest that SFN could provide a novel avenue for preventing and treating ASD, and its therapeutic effects might be related to gut microbiota.

摘要

引言

已发现萝卜硫素(SFN)可通过调节肠道微生物群(GM)减轻与多种疾病相关的并发症,而GM对SFN治疗自闭症谱系障碍(ASD)的影响尚未得到研究。因此,本研究旨在通过动物模型和人体研究来探究SFN对儿童ASD的影响与GM之间的关系。

方法

我们分别使用三室社交测试和俄亥俄州立大学自闭症评定量表 - 第四版(OARS - 4)评估了SFN对母体免疫激活(MIA)诱导的ASD样大鼠模型和儿科自闭症患者的治疗效果,并使用16SrRNA测序进行平行的GM分析。

结果

在三室测试中,SFN显著提高了ASD样大鼠的嗅探时间。对于人类参与者,SFN组的平均言语或非言语交流(OSU - CO)得分在12周终点时发生了显著变化。服用SFN后是安全的,没有严重副作用。ASD样大鼠和ASD患者的GM变化相似,例如在目、科和属水平上的一致变化。虽然在接受SFN治疗的ASD样大鼠中肠道微生物群组成发生了显著改变,但在接受SFN治疗12周后的ASD患者中GM的改变并不明显。然而在网络分析中,我们发现25个分类单元与大鼠社交行为相关,其中8个与ASD样大鼠的SFN治疗有关;对于ASD患者而言,我们发现35个GM丰度改变与SFN治疗后ASD症状的改善相关。此外,在ASD样大鼠和ASD患者的网络分析中均发现科和属与SFN给药有关。

讨论

这些发现表明,SFN可为预防和治疗ASD提供一条新途径,其治疗效果可能与肠道微生物群有关。

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