The Formation of Glycan-Specific Natural Antibodies Repertoire in GaIT-KO Mice Is Determined by Gut Microbiota
The Formation of Glycan-Specific Natural Antibodies Repertoire in GaIT-KO Mice Is Determined by Gut Microbiota
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DOI：
10.3389/fimmu.2019.00342
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发表时间：
2019-03-05
影响因子：
7.3
通讯作者：
Manez, Rafael
中科院分区：
文献类型：
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作者：
Bello-Gil, Daniel;Audebert, Christophe;Manez, Rafael
肠道共生细菌在调节先天性和获得性免疫动态平衡方面具有重要作用。肠道微生物组成的变化与几种疾病状态有关，包括自身免疫和炎症条件。然而，目前还不完全清楚共生肠道微生物区系如何调节和促进系统免疫，以及宿主免疫系统的循环元件是否可以调节微生物群。因此，我们通过元遗传学高通量测序(16S rRNA基因，可变区V3-V5)，研究了近交系GATIT-KO小鼠7个月肠道微生物区系中特定类群的多样性和丰度。通过印刷的糖链阵列技术获得的糖链特异性天然抗体，然后通过全基因组关联研究(MWAS)与每种动物的微生物多样性相关联。我们的数据显示，梭状芽胞杆菌(最丰富的)、细菌目、乳杆菌目和去铁菌目可能与GATIT-KO小鼠天然抗多糖抗体的最终库的发展有关。微生物区系多样性的主要变化(2个月和3个月)与这些小鼠的天然抗多糖抗体水平和谱系的重要变化有关。此外，还发现肠道微生物区系与特定的抗多糖抗体模式之间存在显著的正相关和负相关。就个体特征而言，肠道微生物区系和相应的天然抗多糖抗体谱系在被检查的动物中表现出差异。我们还在不同的分类群中发现了与特定抗糖蛋白抗体的发展相关的冗余。因此，微生物多样性的差异并不一定影响步态KO小鼠肠道微生物组的总体功能输出。综上所述，天然抗碳水化合物抗体的能力可能部分取决于每只步态KO小鼠肠道细菌群产生的持续抗原刺激。肠道微生物区系多样性的微小差异可能决定天然抗多糖抗体的不同谱系和水平，从而可能引起对病原体或其他潜在威胁的不同免疫反应。
Gut commensal bacteria are known to have a significant role in regulating the innate and adaptive immune homeostasis. Alterations in the intestinal microbial composition have been associated with several disease states, including autoimmune and inflammatory conditions. However, it is not entirely clear how commensal gut microbiota modulate and contribute to the systemic immunity, and whether circulating elements of the host immune system could regulate the microbiome. Thus, we have studied the diversity and abundance of specific taxons in the gut microbiota of inbred GaIT-KO mice during 7 months of animal life by metagenetic high-throughput sequencing (16S rRNA gene, variable regions V3-V5). The repertoire of glycan-specific natural antibodies, obtained by printed glycan array technology, was then associated with the microbial diversity for each animal by metagenome-wide association studies (MWAS). Our data show that the orders clostridiales (most abundant), bacteriodales, lactobacillales, and deferribacterales may be associated with the development of the final repertoire of natural anti-glycan antibodies in GaIT-KO mice. The main changes in microbiota diversity (month-2 and month-3) were related to important changes in levels and repertoire of natural anti-glycan antibodies in these mice. Additionally, significant positive and negative associations were found between the gut microbiota and the pattern of specific anti-glycan antibodies. Regarding individual features, the gut microbiota and the corresponding repertoire of natural anti-glycan antibodies showed differences among the examined animals. We also found redundancy in different taxa associated with the development of specific anti-glycan antibodies. Differences in microbial diversity did not, therefore, necessarily influence the overall functional output of the gut microbiome of GaIT-KO mice. In summary, the repertoire of natural anti-carbohydrate antibodies may be partially determined by the continuous antigenic stimulation produced by the gut bacterial population of each GaIT-KO mouse. Small differences in gut microbiota diversity could determine different repertoire and levels of natural anti-glycan antibodies and consequently might induce different immune responses to pathogens or other potential threats.