Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice.
Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice.
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DOI：
10.33696/neurol.2.044
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Schwulst SJ
中科院分区：
文献类型：
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作者：
Davis BT 4th;Islam MBAR;Das P;Gilbert JA;Ho KJ;Schwulst SJ
颅脑损伤的发病年龄呈双峰分布，24岁和65岁为发病高峰，老年人群预后较差。很少有研究明确将受伤时的年龄作为与脑外伤相关的继发性病理的独立生物学变量。在我们已发表的工作框架内，确定了脑外伤对神经病理、认知、记忆和运动功能的年龄相关影响，我们分析了从年轻和老年脑损伤动物身上收集的粪便颗粒，以评估脑外伤引起的代谢失调中年龄诱导的影响。在这项后续工作中，我们假设脑外伤后老年(80周龄，N=10)和年轻(14周龄，N=10)小鼠的生物失调加剧。C57BL/6雄性大鼠接受开颅头控制皮质撞击的假手术或颅脑损伤。分别于伤前1天、伤后1天、7天和28天采集新鲜粪便颗粒，进行16S rRNA基因测序和分类分析。数据显示，随着年龄的增长，与疾病相关的微生物种类增加，而伤害会加剧这种现象。与我们的假设一致，老龄小鼠在损伤前和损伤后表现出大量与疾病相关的肠道微生物群变化。我们的数据表明，年轻人和老年人之间的损伤微生物组表型不同，反映了年龄、脑外伤和肠道-脑轴之间以前未知的相互作用，这意味着需要不同的治疗策略。
Traumatic brain injury (TBI) has a bimodal age distribution with peak incidence at age 24 and age 65 with worse outcomes developing in aged populations. Few studies have specifically addressed age at the time of injury as an independent biologic variable in TBI-associated secondary pathology. Within the framework of our published work, identifying age related effects of TBI on neuropathology, cognition, memory and motor function we analyzed fecal pellets collected from young and aged TBI animals to assess for age-induced effects in TBI induced dysbiosis. In this follow up, work we hypothesized increased dysbiosis after TBI in aged (80-week-old, N=10) versus young (14-week-old, N=10) mice. C57BL/6 males received a sham incision or TBI via open-head controlled cortical impact. Fresh stool pellets were collected 1-day pre-TBI, then 1, 7, and 28-days post-TBI for 16S rRNA gene sequencing and taxonomic analysis. Data revealed an age induced increase in disease associated microbial species which were exacerbated by injury. Consistent with our hypothesis, aged mice demonstrated a high number of disease associated changes to the gut microbiome pre- and post-injury. Our data suggest divergent microbiome phenotypes in injury between young and aged reflecting a previously unknown interaction between age, TBI, and the gut-brain axis implying the need for different treatment strategies.