Multi-Omics Analysis Revealed Characterization of Gastric Microbiome and Metabolome in Helicobacter pylori-Induced Progression of MASLD

Background

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.

Methods

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.

Results

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.

Conclusion

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.