王娟+康禹:新方法揭示自闭症肠道菌群的“新”问题
  • 提出一种类配对队列策略,将肠道菌群代谢背景相似的自闭症(ASD)患儿和正常儿童进行配对比较,以鉴定ASD相关的菌群代谢通路;
  • ASD菌群在解毒的酶和通路方面有明显缺陷,主要涉及谷胱甘肽(关键的抗氧化剂和解毒酶辅因子)生成和有机毒素降解;
  • 这些解毒酶的丰度与线粒体功能紊乱标志物负相关,提示菌群解毒功能对线粒体有潜在保护作用;
  • 基于这些酶的的诊断模型能准确区分ASD和正常儿童(AUC 0.88),且诊断分数与ASD临床评分相关。
主编推荐语
mildbreeze
自闭症谱系障碍(ASD)与肠道菌群失调密切相关,但确切机制并不清楚。由于肠道菌群非常复杂、个体差异很大,对比疾病人群和健康人群的分析方法有时难以排除干扰去找到真正与疾病相关的菌群特征。北京大学医学部孤独症研究中心王娟、中科院北京基因组研究所康禹与团队在Science Advances发表的一项最新研究中,提出了一种“类配对”(quasi-paired)队列研究策略,能将原本的队列转化为配对队列,不仅控制了个体多样性,而且增加了统计功效。通过这种方法,他们挖掘出与ASD高度相关的菌群代谢功能特征,表明ASD患儿存在菌群解毒能力不足的问题,这可能造成了内/外源性毒素在体内的积累,从而导致发生ASD的一个主要病理变化——线粒体功能紊乱。此外,基于ASD相关微生物解毒酶的诊断模型可以较好的分辨出ASD患儿,并与ASD临床评分存在一定关联。这些发现阐释了肠道菌群在ASD发病机制中的一种新作用,提示旨在恢复菌群解毒功能的干预方法或能用于治疗ASD,该研究提出的类配对队列策略,对于进行疾病相关菌群研究也有重要参考意义。
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Science Advances [IF:13.116]

A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

一种类配对队列策略揭示出自闭症儿童肠道微生物的解毒功能受损

10.1126/sciadv.aba3760

2020-10-21, Article

Abstract & Authors:展开

Abstract:收起
Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy—quasi-paired cohort—and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD.

First Authors:
Mengxiang Zhang,Yanan Chu,Qingren Meng

Correspondence Authors:
Yu Kang,Juan Wang

All Authors:
Mengxiang Zhang,Yanan Chu,Qingren Meng,Rui Ding,Xing Shi,Zuqun Wang,Yi He,Juan Zhang,Jing Liu,Jie Zhang,Jun Yu,Yu Kang,Juan Wang

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自闭症医学进展微信公众号

王娟+康禹团队发现孤独症致病新机制

2020-10-22

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