Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
Department of Biotechnology, Vavilov Institute of General Genetics Russian Academy of Sciences, Moscow, Russia.
Front Immunol. 2020 Nov 16;11:595877. doi: 10.3389/fimmu.2020.595877. eCollection 2020.
As permanent residents of the normal gut microbiota, bifidobacteria have evolved to adapt to the host's immune response whose priority is to eliminate pathogenic agents. The mechanisms that ensure the survival of commensals during inflammation and maintain the stability of the core component of the normal gut microbiota in such conditions remain poorly understood. We propose a new approach to study the mechanisms of resistance to immune response factors based on high-throughput sequencing followed by transcriptome analysis. This approach allowed us to detect differentially expressed genes associated with inflammation. In this study, we demonstrated that the presence of the pro-inflammatory cytokines IL-6 and TNFα to the growth medium of the GT15 strain changes the latter's growth rate insignificantly while affecting the expression of certain genes. We identified these genes and performed a COG and a KEGG pathway enrichment analysis. Using phylogenetic profiling we predicted the operons of genes whose expression was triggered by the cytokines TNFα and IL-6 . By mapping the transcription start points, we experimentally validated the predicted operons. Thus, in this study, we predicted the genes involved in a putative signaling pathway underlying the mechanisms of resistance to inflammatory factors in bifidobacteria. Since bifidobacteria are a major component of the human intestinal microbiota exhibiting pronounced anti-inflammatory properties, this study is of great practical and scientific relevance.
作为肠道正常菌群的常驻居民,双歧杆菌已经进化到能够适应宿主的免疫反应,其首要任务是消除病原体。然而,在炎症期间确保共生菌存活并维持正常肠道菌群核心成分稳定性的机制仍知之甚少。我们提出了一种新的方法,基于高通量测序和转录组分析来研究抵抗免疫反应因素的机制。这种方法使我们能够检测与炎症相关的差异表达基因。在这项研究中,我们证明了促炎细胞因子 IL-6 和 TNFα 存在于 GT15 菌株的生长培养基中,虽然对后者的生长速度影响不大,但会影响某些基因的表达。我们确定了这些基因,并进行了 COG 和 KEGG 途径富集分析。使用系统发育分析,我们预测了细胞因子 TNFα 和 IL-6 触发表达的基因操纵子。通过映射转录起始点,我们实验验证了预测的操纵子。因此,在这项研究中,我们预测了参与双歧杆菌抵抗炎症因子机制的潜在信号通路的基因。由于双歧杆菌是人类肠道菌群的主要组成部分,具有明显的抗炎特性,因此这项研究具有重要的实际和科学意义。