Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders
Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders
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DOI：
10.1016/j.anaerobe.2017.12.007
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发表时间：
2018-02-01
期刊：
影响因子：
2.3
通讯作者：
Krajmalnik-Brown, Rosa
中科院分区：
文献类型：
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作者：
Kang, Dae-Wook;Ilhan, Zehra Esra;Krajmalnik-Brown, Rosa
在ASD的人类和动物模型中，支持肠道问题与ASD症状相关的证据越来越多。肠道微生物及其代谢物可能不仅与胃肠道问题有关，而且与ASD行为症状有关。尽管有如此高的兴趣，但大多数先前的研究主要关注微生物结构，并且在ASD背景下对粪便代谢物的研究很少。因此，我们的目的是检测21名ASD儿童和23名神经正常儿童之间可能存在显著不同浓度的粪便代谢物，并研究其与人类肠道微生物群的可能联系。利用h -1核磁共振光谱和16S rRNA基因扩增子测序，我们分别检测了粪便样品中的代谢物谱和微生物组成。在检测到的59种代谢物中，经过多次检测校正后，ASD儿童粪便中的异丙醇浓度显著升高。我们还观察到与先前研究相似的粪便代谢物趋势：ASD儿童的粪便对甲酚浓度较高，GABA浓度可能较低。此外，Fisher判别分析（FDA）表明，一组代谢物——巯基酸盐、烟酸盐、谷氨酰胺、胸腺嘧啶和天冬氨酸——可能作为一种适度的生物标志物，将ASD患者与神经正常组区分开来（78%的敏感性和81%的特异性）。与我们之前的亚利桑那队列研究一致，我们也证实了ASD儿童肠道微生物多样性降低，与copri普雷沃氏菌最密切相关的种型相对丰度降低。经过多次检测校正，我们还了解到，在ASD儿童的粪便中，prausnitzii粪杆菌和副流感嗜血杆菌的相对丰度较低。尽管粪便代谢物的清单相对较短，但本研究的数据支持ASD儿童与神经正常儿童相比，粪便代谢物谱发生了变化，值得在更大的队列中进一步研究代谢物。(C) 2017 Elsevier Ltd.版权所有。
Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using H-1-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies: children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts. (C) 2017 Elsevier Ltd. All rights reserved.