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Abstract：
Streptococcus gordonii (S. gordonii, Sg) is one of the early colonizing, supragingival commensal bacterium normally associated with oral health in human dental plaque. MicroRNAs (miRNAs) play an important role in the inflammation-mediated pathways and are involved in periodontal disease (PD) pathogenesis. PD is a polymicrobial dysbiotic immune-inflammatory disease initiated by microbes in the gingival sulcus/pockets. The objective of this study is to determine the global miRNA expression kinetics in S. gordonii DL1-infected C57BL/6J mice. All mice were randomly divided into four groups (n = 10 mice/group; 5 males and 5 females). Bacterial infection was performed in mice at 8 weeks and 16 weeks, mice were euthanized, and tissues harvested for analysis. We analyzed differentially expressed (DE) miRNAs in the mandibles of S. gordonii-infected mice. Gingival colonization/infection by S. gordonii and alveolar bone resorption (ABR) was confirmed. All the S. gordonii-infected mice at two specific time points showed bacterial colonization (100%) in the gingival surface, and a significant increase in mandible and maxilla ABR (p < 0.0001). miRNA profiling revealed 191 upregulated miRNAs (miR-375, miR-34b-5p) and 22 downregulated miRNAs (miR-133, miR-1224) in the mandibles of S. gordonii-infected mice at the 8-week mark. Conversely, at 16 weeks post-infection, 10 miRNAs (miR-1902, miR-203) were upregulated and 32 miRNAs (miR-1937c, miR-720) were downregulated. Two miRNAs, miR-210 and miR-423-5p, were commonly upregulated, and miR-2135 and miR-145 were commonly downregulated in both 8- and 16-week-infected mice mandibles. Furthermore, we employed five machine learning (ML) algorithms to assess how the number of miRNA copies correlates with S. gordonii infections in mice. In the ML analyses, miR-22 and miR-30c (8-week), miR-720 and miR-339-5p (16-week), and miR-720, miR-22, and miR-339-5p (combined 8- and 16-week) emerged as the most influential miRNAs.
摘要：
格氏链球菌（S.gordonii,Sg）是早期的殖民者之一，牙龈上共生细菌通常与人类牙菌斑中的口腔健康有关。MicroRNAs(miRNAs)在炎症介导的通路中起重要作用,并参与牙周病(PD)的发病机制。PD是由龈沟/袋中的微生物引发的多微生物失调性免疫炎性疾病。本研究的目的是确定格氏链球菌DL1感染的C57BL/6J小鼠中的全局miRNA表达动力学。将所有小鼠随机分为四组(n=10只小鼠/组;5只雄性和5只雌性)。在8周和16周时对小鼠进行细菌感染，小鼠被安乐死，和组织收获分析。我们分析了S.gordonii感染小鼠下颌骨中差异表达(DE)的miRNA。证实了gordonii和牙槽骨吸收（ABR）的牙龈定植/感染。在两个特定的时间点，所有的gordonii感染的小鼠都显示出牙龈表面的细菌定植（100％），下颌骨和上颌骨ABR显着增加（p<0.0001）。miRNA分析显示，在8周标记时，在格氏链球菌感染的小鼠下颌骨中，有191个上调的miRNA（miR-375，miR-34b-5p）和22个下调的miRNA（miR-133，miR-1224）。相反，在感染后16周，10个miRNAs（miR-1902，miR-203）上调，32个miRNAs（miR-1937c，miR-720）下调。两个miRNA,miR-210和miR-423-5p,通常被上调，miR-2135和miR-145在8周和16周感染的小鼠下颌骨中普遍下调。此外，我们采用了5种机器学习(ML)算法来评估小鼠中miRNA拷贝数与S.gordonii感染的相关性.在ML分析中，miR-22和miR-30c（8周），miR-720和miR-339-5p（16周），和miR-720，miR-22和miR-339-5p（组合8周和16周）成为最有影响力的miRNA。
