Spinal Cord Injury Changes the Structure and Functional Potential of Gut Bacterial and Viral Communities.
Spinal Cord Injury Changes the Structure and Functional Potential of Gut Bacterial and Viral Communities.
复制标题
DOI：
10.1128/msystems.01356-20
复制
发表时间：
2021-05-11
期刊：
影响因子：
6.4
通讯作者：
Popovich PG
中科院分区：
文献类型：
--
作者：
Du J;Zayed AA;Kigerl KA;Zane K;Sullivan MB;Popovich PG
据我们所知，这是第一篇应用宏基因组学来表征由临床相关的中枢神经系统（CNS）创伤模型引起的肠道微生物种群动力学变化的文章。它还利用了基因组解析宏基因组学和病毒组学中最新的方法，以最大限度地提高从这些数据中可以做出的生物学推断。新出现的数据表明，肠道生态失调有助于许多人类疾病，包括创伤性脊髓损伤（SCI）后发展的几种合并症。迄今为止，SCI诱导的肠道生态失调的所有分析都使用了16 S rRNA扩增子测序。这种技术有几个局限性，包括易受分类学“盲点”、引物偏倚的影响，以及无法分析微生物群功能或识别病毒。在这里，SCI诱导的肠道生态失调通过应用基因组和基因分辨的宏基因组分析在第4胸椎（T4）或第10胸椎（T10）脊髓水平实验性SCI后21天收集的小鼠粪便样本进行评估。这些不同的损伤部分（T10）或完全（T4）消除了肠道中的交感神经张力。在细菌中，回收了105个中等质量至高质量的宏基因组组装基因组（MAG），其中大多数（n = 96）代表新的细菌物种。Read作图显示，SCI后，有益菌（约氏乳杆菌和CAG-1031 spp.）减少，而潜在致病菌（Weissella cibaria，Lactococcus lactis_A，Bacteroides thetaiotaomicron）增加。在功能上，编码色氨酸、维生素B6和叶酸生物合成蛋白质的微生物基因在SCI后减少，这些蛋白质是中枢神经系统功能的重要途径。在病毒中，回收了1，028种主要是新型病毒群体，与公共数据库相比，将已知的小鼠肠道病毒物种序列空间扩展了1.3倍。脊髓损伤后，有益宿主（CAG-1031、乳杆菌和Turicibacter）的噬菌体减少，而致病宿主（Weissella、乳球菌和梭菌）的噬菌体增加。尽管所有SCI小鼠的微生物组和病毒组都发生了变化，但其中一些变化随着脊髓损伤水平的变化而变化，这表明交感神经张力的丧失是肠道生态失调的潜在机制。重要性据我们所知，这是第一篇应用宏基因组学来表征由临床相关的中枢神经系统（CNS）创伤模型引起的肠道微生物种群动力学变化的文章。它还利用了基因组解析宏基因组学和病毒组学中最新的方法，以最大限度地提高从这些数据中可以做出的生物学推断。总的来说，这篇文章强调了创伤性脊髓损伤（SCI）后远端器官（肠道）及其微生物组居民的自主神经系统调节的重要性。通过提供分类学、功能和病毒的信息，宏基因组数据可以更好地预测SCI诱导的肠道生态失调如何影响SCI后的系统和神经结局。
To our knowledge, this is the first article to apply metagenomics to characterize changes in gut microbial population dynamics caused by a clinically relevant model of central nervous system (CNS) trauma. It also utilizes the most current approaches in genome-resolved metagenomics and viromics to maximize the biological inferences that can be made from these data. Emerging data indicate that gut dysbiosis contributes to many human diseases, including several comorbidities that develop after traumatic spinal cord injury (SCI). To date, all analyses of SCI-induced gut dysbiosis have used 16S rRNA amplicon sequencing. This technique has several limitations, including being susceptible to taxonomic “blind spots,” primer bias, and an inability to profile microbiota functions or identify viruses. Here, SCI-induced gut dysbiosis was assessed by applying genome- and gene-resolved metagenomic analysis of murine stool samples collected 21 days after an experimental SCI at the 4th thoracic spine (T4) or 10th thoracic spine (T10) spinal level. These distinct injuries partially (T10) or completely (T4) abolish sympathetic tone in the gut. Among bacteria, 105 medium- to high-quality metagenome-assembled genomes (MAGs) were recovered, with most (n = 96) representing new bacterial species. Read mapping revealed that after SCI, the relative abundance of beneficial commensals (Lactobacillus johnsonii and CAG-1031 spp.) decreased, while potentially pathogenic bacteria (Weissella cibaria, Lactococcus lactis_A, Bacteroides thetaiotaomicron) increased. Functionally, microbial genes encoding proteins for tryptophan, vitamin B6, and folate biosynthesis, essential pathways for central nervous system function, were reduced after SCI. Among viruses, 1,028 mostly novel viral populations were recovered, expanding known murine gut viral species sequence space ∼3-fold compared to that of public databases. Phages of beneficial commensal hosts (CAG-1031, Lactobacillus, and Turicibacter) decreased, while phages of pathogenic hosts (Weissella, Lactococcus, and class Clostridia) increased after SCI. Although the microbiomes and viromes were changed in all SCI mice, some of these changes varied as a function of spinal injury level, implicating loss of sympathetic tone as a mechanism underlying gut dysbiosis. IMPORTANCE To our knowledge, this is the first article to apply metagenomics to characterize changes in gut microbial population dynamics caused by a clinically relevant model of central nervous system (CNS) trauma. It also utilizes the most current approaches in genome-resolved metagenomics and viromics to maximize the biological inferences that can be made from these data. Overall, this article highlights the importance of autonomic nervous system regulation of a distal organ (gut) and its microbiome inhabitants after traumatic spinal cord injury (SCI). By providing information on taxonomy, function, and viruses, metagenomic data may better predict how SCI-induced gut dysbiosis influences systemic and neurological outcomes after SCI.