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癫痫患者肠道微生物群的改变及作为生物标志物的潜在指标

Alteration of Gut Microbiota in Patients With Epilepsy and the Potential Index as a Biomarker.

作者信息

Gong Xue, Liu Xu, Chen Chu, Lin Jingfang, Li Aiqing, Guo Kundian, An Dongmei, Zhou Dong, Hong Zhen

机构信息

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Microbiol. 2020 Sep 18;11:517797. doi: 10.3389/fmicb.2020.517797. eCollection 2020.

DOI:10.3389/fmicb.2020.517797
PMID:33042045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7530173/
Abstract

OBJECTIVE

To explore the structure and composition of the fecal microbiota of patients with epilepsy.

METHODS

Variations in the fecal microbiota between patients with epilepsy and healthy controls (HCs) from the same household were investigated and validated by utilizing 16S ribosomal RNA sequencing in two independent cohorts [exploration cohort ( = 55 patients and = 46 HCs) and validation cohort ( = 13 patients and = 10 HCs)].

RESULTS

The alpha diversity indexes of the specimens from patients with epilepsy were much lower than those from the HCs ( < 0.05). The structure and composition of the fecal microbiota differed between patients with different clinical prognoses and between patients and HCs (Adonis: < 0.05). Microbiome alterations in patients with epilepsy included increases in and and decreases in at the phylum level and increases in , , , and others at the genus level [linear discriminant analysis (LDA): 3.5] Patients with drug-resistant epilepsy showed enrichment of bacterial taxa in , , and and the genera , , , , and (Kruskal-Wallis test: < 0.05). Analysis of gut microbiome indicated predictive ability for disease diagnosis, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.97 (95% CI, 0.84-0.98). Applying the model to our validation cohort resulted in an AUC of 0.96 (95% CI, 0.75-0.97). Notably, the model could distinguish drug-resistant from drug-sensitive epilepsy (AUC = 0.85, 95% CI: 0.69-0.94).

CONCLUSION

Patients with epilepsy exhibit substantial alterations of fecal microbiota composition, and specific gut commensal strains are altered depending on different clinical phenotypes and thus could serve as potential biomarkers for disease diagnosis.

摘要

目的

探讨癫痫患者粪便微生物群的结构和组成。

方法

利用16S核糖体RNA测序技术,在两个独立队列[探索队列(55例患者和46例健康对照)和验证队列(13例患者和10例健康对照)]中,研究并验证了癫痫患者与来自同一家庭的健康对照(HCs)之间粪便微生物群的差异。

结果

癫痫患者标本的α多样性指数远低于健康对照(P<0.05)。不同临床预后的患者之间以及患者与健康对照之间粪便微生物群的结构和组成存在差异(Adonis检验:P<0.05)。癫痫患者的微生物组改变包括门水平上拟杆菌门和变形菌门增加、厚壁菌门减少,以及属水平上普雷沃菌属、瘤胃球菌属、粪杆菌属等增加[线性判别分析(LDA):3.5]。耐药性癫痫患者的细菌类群在放线菌门、变形菌门和厚壁菌门以及普雷沃菌属、韦荣球菌属、瘤胃球菌属、粪杆菌属和双歧杆菌属中富集(Kruskal-Wallis检验:P<0.05)。肠道微生物组分析表明其对疾病诊断具有预测能力,受试者操作特征(ROC)曲线下面积(AUC)为0.97(95%CI,0.84-0.98)。将该模型应用于我们的验证队列,AUC为0.96(95%CI,0.75-0.97)。值得注意的是,该模型可以区分耐药性癫痫和药物敏感性癫痫(AUC = 0.85,95%CI:0.69-0.94)。

结论

癫痫患者的粪便微生物群组成存在显著改变,特定的肠道共生菌株根据不同的临床表型而改变,因此可作为疾病诊断的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/73955d52f584/fmicb-11-517797-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/26a66bf473ab/fmicb-11-517797-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/0154d8149f40/fmicb-11-517797-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/576e49760b9f/fmicb-11-517797-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/8be5e2f71621/fmicb-11-517797-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/73955d52f584/fmicb-11-517797-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/26a66bf473ab/fmicb-11-517797-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/0154d8149f40/fmicb-11-517797-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/576e49760b9f/fmicb-11-517797-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/8be5e2f71621/fmicb-11-517797-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a8/7530173/73955d52f584/fmicb-11-517797-g005.jpg

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