创伤性脑损伤后易患癫痫与预先存在的肠道微生物组特征有关。
Susceptibility to epilepsy after traumatic brain injury is associated with preexistent gut microbiome profile.
机构信息
Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.
Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.
出版信息
Epilepsia. 2022 Jul;63(7):1835-1848. doi: 10.1111/epi.17248. Epub 2022 Apr 16.
OBJECTIVE
We examined whether posttraumatic epilepsy (PTE) is associated with measurable perturbations in gut microbiome.
METHODS
Adult Sprague Dawley rats were subjected to lateral fluid percussion injury (LFPI). PTE was examined 7 months after LFPI, during 4-week continuous video-electroencephalographic monitoring. 16S ribosomal RNA gene sequencing was performed in fecal samples collected before LFPI/sham-LFPI and 1 week, 1 month, and 7 months thereafter. Longitudinal analyses of alpha diversity, beta diversity, and differential microbial abundance were performed. Short-chain fatty acids (SCFAs) were measured in fecal samples collected before LFPI by liquid chromatography with tandem mass spectrometry.
RESULTS
Alpha diversity changed over time in both LFPI and sham-LFPI subjects; no association was observed between alpha diversity and LFPI, the severity of post-LFPI neuromotor impairments, and PTE. LFPI produced significant changes in beta diversity and selective changes in microbial abundances associated with the severity of neuromotor impairments. No association between LFPI-dependent microbial perturbations and PTE was detected. PTE was associated with beta diversity irrespective of timepoint vis-à-vis LFPI, including at baseline. Preexistent fecal microbial abundances of four amplicon sequence variants belonging to the Lachnospiraceae family (three enriched and one depleted) predicted the risk of PTE, with area under the curve (AUC) of .73. Global SCFA content was associated with the increased risk of PTE, with AUC of .722, and with 2-methylbutyric (depleted), valeric (depleted), isobutyric (enriched), and isovaleric (enriched) acids being the most important factors (AUC = .717). When the analyses of baseline microbial and SCFA compositions were combined, AUC to predict PTE increased to .78.
SIGNIFICANCE
Whereas LFPI produces no perturbations in the gut microbiome that are associated with PTE, the risk of PTE can be stratified based on preexistent microbial abundances and SCFA content.
目的
我们研究了创伤后癫痫（PTE）是否与肠道微生物组的可测量扰动有关。
方法
成年 Sprague Dawley 大鼠接受侧方液压冲击伤（LFPI）。在 LFPI 后 7 个月，通过连续 4 周的视频-脑电图监测检查 PTE。在 LFPI/假 LFPI 之前和之后的 1 周、1 个月和 7 个月采集粪便样本进行 16S 核糖体 RNA 基因测序。进行 alpha 多样性、beta 多样性和差异微生物丰度的纵向分析。通过液相色谱-串联质谱法在 LFPI 之前采集粪便样本测量短链脂肪酸（SCFA）。
结果
LFPI 和假 LFPI 受试者的 alpha 多样性随时间发生变化；alpha 多样性与 LFPI、LFPI 后神经运动障碍的严重程度以及 PTE 之间无相关性。LFPI 导致 beta 多样性发生显著变化，并与神经运动障碍严重程度相关的微生物丰度发生选择性变化。未检测到 LFPI 依赖性微生物扰动与 PTE 之间存在相关性。PTE 与 LFPI 相关的 beta 多样性有关，无论时间点如何，包括基线。属于 Lachnospiraceae 家族的四个扩增子序列变体（三个富集和一个耗尽）的粪便微生物丰度与 PTE 的风险相关，曲线下面积（AUC）为.73。总 SCFA 含量与 PTE 的高风险相关，AUC 为.722，其中 2-甲基丁酸（耗尽）、戊酸（耗尽）、异丁酸（富集）和异戊酸（富集）是最重要的因素（AUC =.717）。当结合基线微生物和 SCFA 组成的分析时，预测 PTE 的 AUC 增加到.78。
意义
尽管 LFPI 对肠道微生物组没有产生与 PTE 相关的扰动，但可以根据预先存在的微生物丰度和 SCFA 含量对 PTE 的风险进行分层。
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