Combined Methylation and Transcriptome Analysis of Liver Injury of Nonalcoholic Fatty Liver Disease Induced by High Alcohol-Producing Klebsiella Pneumoniae

Overview

Journal Microbiol Spectr

Specialty Microbiology

Date 2023 Apr 6

PMID 37022192

Authors

Rui Zhang

Ziying Xu

Guanhua Xue

Junxia Feng

Bing Du

Lin Gan

Zheng Fan

Tongtong Fu

Yanling Feng

Hanqing Zhao

Jinghua Cui

Chao Yan

Xiaohu Cui

Ziyan Tian

Jinfeng Chen

Zihui Yu

Jing Yuan

Affiliations

Soon will be listed here.

Abstract

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.

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