Department of Gastroenterology, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Changsha, 410011, Hunan Province, China.
Research Center of Digestive Diseases, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, Hunan Province, China.
J Transl Med. 2024 Jul 29;22(1):701. doi: 10.1186/s12967-024-05506-y.
The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has 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 MASLD.
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.
Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the "nonalcoholic fatty liver disease" pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups 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. DEG enrichment pathways were concentrated in the "PPAR pathway" and "fatty acid degradation."
Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.
幽门螺杆菌（H. pylori）感染与代谢相关脂肪性肝病（MASLD）的关系已引起临床关注。然而，目前大多数研究涉及横断面研究和荟萃分析，实验机制探索仍有待改进。本研究旨在探讨 H. pylori 影响 MASLD 的机制。
我们建立了两种 H. pylori 感染（Cag A 阳性和 Cag A 阴性）的小鼠模型，分别给予 16 周的标准饮食（CD）或高脂饮食（HFD）喂养。测量体重、肝甘油三酯、血糖、血清生化参数、炎症因子和胰岛素抵抗，并进行肝组织学分析。对小鼠肝脏进行转录组 RNA 测序分析。
虽然 H. pylori 感染不能显著影响 CD 模式下小鼠的血清炎症因子水平和血清生化参数，但血清胰岛素和稳态模型评估的胰岛素抵抗水平升高。相比之下，H. pylori Cag A+感染显著加重了 HFD 诱导的肝组织病理学脂肪变性，并升高了血清炎症因子和脂质代谢参数。在 CD 组中，H. pylori Cag A+感染组有 767 个差异表达基因（DEGs），H. pylori Cag A-感染组有 1473 个 DEGs，KEGG 分析显著富集了“非酒精性脂肪性肝病”途径。在 H. pylori Cag A+感染合并 HFD 喂养组中，有 578 个 DEGs，在 H. pylori Cag A-感染组中，有 820 个 DEGs。HFD 组的 DEGs 显著富集于“脂肪酸降解”和“PPAR 途径”。探究不同 Cag A 状态对小鼠肝脏的影响发现，Cag A- H. pylori 中脂肪酸结合蛋白 5 差异表达。DEG 富集途径集中在“PPAR 途径”和“脂肪酸降解”。
临床医生有望了解 H. pylori 对 MASLD 的影响，更好地理解和管理 MASLD。H. pylori 感染可能通过调节肝脂代谢加重 MASLD 的发生，而 H. pylori 毒力因子 Cag A 在这种调节中起着至关重要的作用。
