Helicobacter pylori infection exacerbates nonalcoholic fatty liver disease through lipid metabolic pathways: a transcriptomic study.

Background The relationship between Helicobacter pylori ( H. pylori ) infection and nonalcoholic fatty liver disease (NAFLD) have attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts NAFLD. Methods We established two H. pylori -infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. Results Although H. pylori infection could not significantly affect serum inflammatory factor levels and mouse liver pathology, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis revealed 767 differentially expressed genes (DEGs) in the H. pylori -infected group in the CD groups, and the "nonalcoholic fatty liver disease" pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori infection combined with the HFD feeding group, and DEGs were significantly enriched in "fatty acid degradation" and "PPAR pathway." Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. Pylori and DEGs enrichment pathways were concentrated in the "PPAR pathway" and "fatty acid degradation." Conclusions H. pylori infection may exacerbate the development of NAFLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.