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Intestinal Microbiota Polymorphism of Epilepsy Patients in Middle and High Altitude Areas: A Case-control Study
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摘要:
目的 探究中高海拔地区癫痫患者肠道菌群组成与分布特征，以期为癫痫病因学研究提供理论依据。 方法 2021年9月至2022年8月，连续招募世居于中高海拔地区(海拔2200~4500 m)癫痫患者(middle-high altitude epilepsy, MHE)和中高海拔地区健康人群(middle-high altitude normal, MHN)。其中MHE来自于青海省人民医院神经内科癫痫患者，MHN来自于青海省人民医院体检中心体检的健康人群，并按照年龄、性别与MHE进行1∶1匹配。收集两组粪便组织标本，对肠道菌群16S rDNA V3~V4区进行DNA测序并进行生物信息学分析。 结果 共入选符合纳入与排除标准的MHE 32例、MHN 33名。α多样性分析显示，MHE组ACE指数、Shannon指数、Chao指数均低于MHN组(P均＜0.05)；β多样性分析显示，二者的肠道菌群分布存在显著差异。在对肠道菌群组成成分的分析中，MHE组在门水平、属水平亦显示出不同于MHN组的特征，其疣微菌门(Verrucomicrobiota)、柯林斯氏菌属(Collinsella)、梭杆菌属(Fusobacteriota)、双歧杆菌属(Bifidobacterium)等菌种的相对丰度增高，拟杆菌门(Bacteroidota)、拟杆菌属(Bacteroides)、普氏菌属(Prevotella)、粪杆菌属(Faecalibacterium)等菌种的相对丰度降低。 结论 中高海拔地区癫痫患者肠道菌群呈现出不同于同海拔健康人群的多态性，可能与癫痫发生具有一定关联性。 Abstract:Objective To investigate the composition and distribution characteristics of intestinal flora in patients with epilepsy at middle-high altitude, in order to provide theoretical reference for the etiological study of epilepsy. Methods From September 2021 to August 2022, we continuously recruited middle-high altitude epilepsy (MHE) patients (altitude 2200-4500 m) and healthy people at the same altitude as middle- high altitude normal (MHN). MHE were epileptic patients in neurology department of Qinghai Provincial People's Hospital, and MHN were healthy people in physical examination center of Qinghai Provincial People's Hospital which matched 1∶1 with MHE by age and gender. Stool tissue specimens from both groups were collected, and the 16S rDNA V3 to V4 regions of the intestinal flora were sequenced for DNA and analyzed bioinformatically. Results A total of 32 cases of MHE and 33 cases of MHN who met the inclusion and exclusion criteria. Alfa diversity analysis showed that ACE index, Shannon index and Chao index in MHE group were lower than those in MHN group (all P < 0.05). Beta diversity analysis showed that there were significant differences in the distribution of intestinal flora between the two groups. In the analysis of intestinal flora composition, MHE group also showed different characteristics from MHN group at phylum level and genus level. The relative abundance of Verrucomicrobiota, Collinsella, Fusobacteriota, Bifidobacterium and other bacteria increased, whereas the relative abundance of Bacteroidota, Bacteroides, Prevotella, Faecalibacterium and other bacteria decreased. Conclusion The intestinal flora of epilepsy patients at middle and high altitude has different polymorphisms from that of healthy people at the same altitude, which may be associated with epilepsy. -
Key words:
- epilepsy /
- intestinal flora /
- middle and high altitude /
- microbiota polymorphism
作者贡献：郑美玲负责标本收集、文献查阅、数据分析及论文撰写；樊青俐负责研究设计与论文修订；钟莲梅负责论文审核。利益冲突：所有作者均声明不存在利益冲突 -
图 1 MHE组和MHN组肠道菌群多样性比较
A.稀疏曲线(Shannon指数)；B.β多样性(主坐标分析)；C.基于加权UniFrac距离矩阵样本树树状图
MHE、MHN：同表 1
图 2 MHE组与MHN组肠道菌群分布特征
A.门水平物种组成柱状图；B.属水平物种组成柱状图；C.门水平物种丰度聚类热图；D.属水平物种丰度聚类热图
MHE、MHN：同表 1表 1 两组基线资料比较
组别 年龄(x±s，岁) 男性[n(%)] BMI (x±s，kg/m2) ALT (x±s，U/L) AST (x±s，U/L) Cr (x±s，μmol/L) TC (x±s，mmol/L) TG (x±s，mmol/L) MHE组(n=32) 38.7±16.81 17(53.1) 22.6±3.27 25.68±12.8 24.59±8.36 78.6±13.02 4.11±0.68 1.35±0.56 MHN组(n=33) 42.3±16.81 20(60.6) 22.7±2.52 29.93±11.6 27.56±8.58 79.5±15.26 4.39±0.76 1.45±0.62 P值 0.383 0.335 0.842 0.455 0.286 0.861 0.482 0.396 MHE：中高海拔地区癫痫患者；MHN：中高海拔地区健康人群；BMI：体质量指数；ALT：谷丙转氨酶；AST：谷草转氨酶；Cr：肌酐；TC：总胆固醇；TG：甘油三酯 
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