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肠道共生真菌失调及其对注意缺陷多动障碍肠道通透性的影响。

Gut mycobiome dysbiosis and its impact on intestinal permeability in attention-deficit/hyperactivity disorder.

机构信息

Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

出版信息

J Child Psychol Psychiatry. 2023 Sep;64(9):1280-1291. doi: 10.1111/jcpp.13779. Epub 2023 Apr 5.

Abstract

BACKGROUND

Dysbiosis in the gut microbial community might be involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The fungal component of the gut microbiome, namely the mycobiota, is a hyperdiverse group of multicellular eukaryotes that can influence host intestinal permeability. This study therefore aimed to investigate the impact of fungal mycobiome dysbiosis and intestinal permeability on ADHD.

METHODS

Faecal samples were collected from 35 children with ADHD and from 35 healthy controls. Total DNA was extracted from the faecal samples and the internal transcribed spacer regions were sequenced using high-throughput next-generation sequencing (NGS). The fungal taxonomic classification was analysed using bioinformatics tools and the differentially expressed fungal species between the ADHD and healthy control groups were identified. An in vitro permeability assay (Caco-2 cell layer) was used to evaluate the biological effects of fungal dysbiosis on intestinal epithelial barrier function.

RESULTS

The β-diversity (the species diversity between two communities), but not α-diversity (the species diversity within a community), reflected the differences in fungal community composition between ADHD and control groups. At the phylum level, the ADHD group displayed a significantly higher abundance of Ascomycota and a significantly lower abundance of Basidiomycota than the healthy control group. At the genus level, the abundance of Candida (especially Candida albicans) was significantly increased in ADHD patients compared to the healthy controls. In addition, the in vitro cell assay revealed that C. albicans secretions significantly enhanced the permeability of Caco-2 cells.

CONCLUSIONS

The current study is the first to explore altered gut mycobiome dysbiosis using the NGS platform in ADHD. The findings from this study indicated that dysbiosis of the fungal mycobiome and intestinal permeability might be associated with susceptibility to ADHD.

摘要

背景

肠道微生物群落的失调可能与注意缺陷多动障碍(ADHD)的病理生理学有关。肠道微生物组的真菌成分,即真菌群,是一组高度多样化的多细胞真核生物,可影响宿主肠道通透性。因此,本研究旨在调查真菌菌群失调和肠道通透性对 ADHD 的影响。

方法

从 35 名 ADHD 儿童和 35 名健康对照者中采集粪便样本。从粪便样本中提取总 DNA,并使用高通量下一代测序(NGS)对内部转录间隔区进行测序。使用生物信息学工具分析真菌分类,并确定 ADHD 组和健康对照组之间差异表达的真菌物种。使用体外通透性测定(Caco-2 细胞层)评估真菌失调对肠道上皮屏障功能的生物学影响。

结果

β多样性(两个群落之间的物种多样性)而不是α多样性(一个群落内的物种多样性)反映了 ADHD 组和对照组之间真菌群落组成的差异。在门水平上,ADHD 组的子囊菌门丰度显著升高,担子菌门丰度显著降低。在属水平上,与健康对照组相比,ADHD 患者的 Candida(尤其是 Candida albicans)丰度显著增加。此外,体外细胞测定显示,C. albicans 的分泌物显著增强了 Caco-2 细胞的通透性。

结论

本研究首次使用 NGS 平台探索 ADHD 中肠道真菌菌群失调。本研究的结果表明,真菌菌群失调和肠道通透性可能与 ADHD 的易感性有关。

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