Capital Institute of Pediatrics, Beijing, China.
Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Microbiol Spectr. 2023 Jun 15;11(3):e0532322. doi: 10.1128/spectrum.05323-22. Epub 2023 Apr 6.
It has been known that high alcohol-producing Klebsiella pneumoniae (HiAlc ) is one of causative agents of nonalcoholic fatty liver disease (NAFLD). However, how HiAlc promotes liver injury remains unclear. Recent findings suggest that DNA methylation might associate with the pathogenesis of NAFLD. Herein, the role of DNA methylation in HiAlc -induced liver injury was investigated. Murine models of NAFLD were established in C57BL/6N wild-type mice by gavaging HiAlc for 8 weeks. The liver injury was assessed based on the liver histopathology and biochemical indicators. In addition, DNA methylation in hepatic tissue was assessed by using dot bolt of 5-mC. RNA sequencing analysis and whole-genome bisulfite sequencing (WGBS) analysis were also performed. HiAlc significantly increased the activity of aspartate transaminase (AST), alanine transaminase (ALT), triglycerides (TGs), and glutathione (GSH), while hypomethylation was associated with liver injury in the experimental mice induced by HiAlc . The GO and KEGG pathway enrichment analysis of the transcriptome revealed that HiAlc induced fat metabolic disorders and DNA damage. The conjoint analysis of methylome and transcriptome showed that hypomethylation regulated related gene expression in signal pathways of lipid formation and circadian rhythm, including and genes, which may be the dominant cause of NAFLD induced by HiAlc . Data suggest that DNA hypomethylation might play an important role in liver injury of NAFLD induced by HiAlc . Which possibly provides a new sight for understanding the mechanisms of NAFLD and selecting the potential therapeutic targets. High alcohol-producing Klebsiella pneumoniae (HiAlc ) is one of causative agents of nonalcoholic fatty liver disease (NAFLD) and could induce liver damage. DNA methylation, as a common epigenetic form following contact with an etiologic agent and pathogenesis, can affect chromosome stability and transcription. We conjointly analyzed DNA methylation and transcriptome levels in the established murine models to explore the potential mechanisms for further understanding the role of DNA methylation in the liver damage of HiAlc -induced NAFLD. The analysis of the DNA methylation landscape contributes to our understanding of the entire disease process, which might be crucial in developing treatment strategies.
已知高产酒精肺炎克雷伯菌（HiAlc）是导致非酒精性脂肪性肝病（NAFLD）的病原体之一。然而，HiAlc 如何促进肝损伤尚不清楚。最近的研究结果表明，DNA 甲基化可能与 NAFLD 的发病机制有关。在此，研究了 DNA 甲基化在 HiAlc 诱导的肝损伤中的作用。通过灌胃 HiAlc 8 周建立 C57BL/6N 野生型小鼠的 NAFLD 模型。基于肝组织病理学和生化指标评估肝损伤。此外，还通过 5-mC 的点印迹法评估肝组织中的 DNA 甲基化。还进行了 RNA 测序分析和全基因组亚硫酸氢盐测序（WGBS）分析。HiAlc 显著增加了天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、甘油三酯（TGs）和谷胱甘肽（GSH）的活性，而低甲基化与实验小鼠的肝损伤有关由 HiAlc 诱导。转录组的 GO 和 KEGG 通路富集分析表明，HiAlc 诱导脂肪代谢紊乱和 DNA 损伤。甲基组和转录组的联合分析表明，低甲基化调节脂质形成和昼夜节律信号通路中相关基因的表达，包括和基因，这可能是 HiAlc 诱导的 NAFLD 的主要原因。数据表明，DNA 低甲基化可能在 HiAlc 诱导的 NAFLD 肝损伤中发挥重要作用。这可能为理解 NAFLD 的机制和选择潜在的治疗靶点提供新的视角。高产酒精肺炎克雷伯菌（HiAlc）是导致非酒精性脂肪性肝病（NAFLD）的病原体之一，可引起肝损伤。DNA 甲基化作为接触病因和发病机制后的一种常见表观遗传形式，可以影响染色体稳定性和转录。我们共同分析了建立的小鼠模型中的 DNA 甲基化和转录组水平，以探讨 DNA 甲基化在 HiAlc 诱导的 NAFLD 肝损伤中的潜在机制。对 DNA 甲基化景观的分析有助于我们全面了解整个疾病过程，这对于制定治疗策略可能至关重要。
