State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Department of Periodontics, Sichuan University, Chengdu, China.
Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Cell Infect Microbiol. 2022 Mar 10;12:776996. doi: 10.3389/fcimb.2022.776996. eCollection 2022.
, a keystone periodontal pathogen, has emerged as a risk factor for systemic chronic diseases, including non-alcoholic fatty liver disease (NAFLD). To clarify the mechanism by which this pathogen induces such diseases, we simultaneously analyzed the transcriptome of intracellular and infected host cells dual RNA sequencing. Pathway analysis was also performed to determine the differentially expressed genes in the infected cells. Further, the infection-induced notable expression of and genes, which participate in branched-chain amino acid (BCAA) transfer, was also analyzed. Furthermore, given that the results of recent studies have associated NAFLD progression with elevated serum BCAA levels, which reportedly, are upregulated by , we hypothesized that this pathogen may induce increases in serum BCAA levels and exacerbate liver injury . To verify this hypothesis, we constructed -deficient strains (, ) and established a high-fat diet (HFD)-fed murine model infected with . Thereafter, the kinetic growth and exopolysaccharide (EPS) production rates as well as the invasion efficiency and colonization of the mutant strains were compared with those of the parental strain. The serum BCAA and fasting glucose levels of the mice infected with either the wild-type or mutant strains, as well as their liver function were also further investigated. It was observed that infection enhanced serum BCAA levels and aggravated liver injury in the HFD-fed mice. Additionally, deletion had no effect on bacterial growth, EPS production, invasion efficiency, and colonization, whereas the strain showed a slight decrease in invasion efficiency and colonization. More importantly, however, both the and h strains showed impaired ability to upregulate serum BCAA levels or exacerbate liver injury in HFD-fed mice. Overall, these results suggested that possibly aggravates NAFLD progression in HFD-fed mice by increasing serum BCAA levels, and this effect showed dependency on the bacterial BCAA transport system.
牙龈卟啉单胞菌是一种关键的牙周病原体，已成为包括非酒精性脂肪性肝病（NAFLD）在内的全身性慢性疾病的危险因素。为了阐明该病原体引起这些疾病的机制，我们同时分析了细胞内和感染宿主细胞的双 RNA 测序转录组。还进行了途径分析，以确定感染细胞中差异表达的基因。此外，还分析了感染诱导的显著表达的 和 基因，这些基因参与支链氨基酸（BCAA）转移。此外，鉴于最近的研究结果将 NAFLD 进展与升高的血清 BCAA 水平相关联，据报道，牙龈卟啉单胞菌上调了这些水平，我们假设该病原体可能导致血清 BCAA 水平升高并加重肝损伤。为了验证这一假设，我们构建了 - 缺陷株（ ， ）并建立了高脂饮食（HFD）喂养感染 的小鼠模型。此后，比较了突变株与亲本株的动力学生长和外多糖（EPS）产生率以及侵袭效率和 定植。还进一步研究了感染野生型或突变株的小鼠的血清 BCAA 和空腹血糖水平及其肝功能。结果表明， 感染增强了 HFD 喂养小鼠的血清 BCAA 水平并加重了肝损伤。此外， 缺失对细菌生长、EPS 产生、侵袭效率和 定植没有影响，而 株的侵袭效率和 定植略有下降。然而，更重要的是， 株和 h 株均显示出降低上调血清 BCAA 水平或加重 HFD 喂养小鼠肝损伤的能力。总体而言，这些结果表明， 可能通过增加血清 BCAA 水平加重 HFD 喂养小鼠的 NAFLD 进展，并且这种作用依赖于细菌的 BCAA 转运系统。
