Chen Han, Wang Yan, Shao Yuting, Su Wei, Li Shuo, Liu Yun, Zhou Xiaoying
Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
The First Clinical Medical College, Nanjing Medical University, Nanjing, China.
Helicobacter. 2025 Sep-Oct;30(5):e70069. doi: 10.1111/hel.70069.
Several clinical studies have demonstrated that Helicobacter pylori (Hp) infection may exacerbate the progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD); however, the underlying mechanisms remain unclear. This study aims to investigate the characterization of the gastric microbiome and metabolome in relation to the progression of MASLD induced by Hp infection.
We established a high-fat diet (HFD) obese mouse model, both with and without Hp infection, to compare alterations in serum and liver metabolic phenotypes. Subsequently, a multi-omics analysis was performed, combining gastric 16S rRNA amplicon sequencing, targeted energy metabolomics, and liver metabolomics sequencing to investigate the correlations among gastric microbiota, energy metabolism, and hepatic metabolism following Hp infection.
HFD mice infected with Hp exhibited a more severe liver steatosis phenotype compared with Hp-negative controls. Hp infection triggers gastric dysbiosis, resulting in a notable enrichment of the Helicobacter genus, which subsequently becomes the dominant bacterial community. This shift leads to a significant rise in the abundance of other bacteria, such as Enterococcus, Streptococcus, and Staphylococcus, while concurrently reducing beneficial bacterial taxa such as Bifidobacterium. Analysis of bacterial functional enrichment and gastric energy metabolomics consistently reveals elevated glycolytic pathway activity in gastric tissue following Hp infection. Furthermore, liver metabolomics indicate increased activities of both glycolytic and lipid metabolic pathways in the liver. The disturbance of the gastric microbiota-metabolism axis is significantly and positively correlated with the hepatic lactate content and severity of hepatic steatosis and inflammation.
Hp infection may influence liver metabolism through microbial-metabolic interactions within the gastrohepatic axis, potentially exacerbating the progression of hepatic steatosis. Further studies are necessary to verify these potential causal relationships.
多项临床研究表明，幽门螺杆菌（Hp）感染可能会加剧代谢功能障碍相关脂肪性肝病（MASLD）的进展；然而，其潜在机制仍不清楚。本研究旨在调查与Hp感染诱导的MASLD进展相关的胃微生物组和代谢组特征。
我们建立了高脂饮食（HFD）肥胖小鼠模型，分为感染Hp和未感染Hp两组，以比较血清和肝脏代谢表型的变化。随后，进行了多组学分析，结合胃16S rRNA扩增子测序、靶向能量代谢组学和肝脏代谢组学测序，以研究Hp感染后胃微生物群、能量代谢和肝脏代谢之间的相关性。
与Hp阴性对照组相比，感染Hp的HFD小鼠表现出更严重的肝脏脂肪变性表型。Hp感染引发胃生态失调，导致螺杆菌属显著富集，随后成为主要细菌群落。这种转变导致其他细菌（如肠球菌、链球菌和葡萄球菌）的丰度显著增加，同时减少了有益细菌类群（如双歧杆菌）。对细菌功能富集和胃能量代谢组学的分析一致显示，Hp感染后胃组织中的糖酵解途径活性升高。此外，肝脏代谢组学表明肝脏中糖酵解和脂质代谢途径的活性均增加。胃微生物群-代谢轴的紊乱与肝脏乳酸含量、肝脂肪变性和炎症的严重程度显著正相关。
Hp感染可能通过肝胃轴内的微生物-代谢相互作用影响肝脏代谢，可能会加剧肝脂肪变性的进展。需要进一步研究来验证这些潜在的因果关系。
