A Bidirectional Association Between Helicobacter pylori Infection and Hyperlipidemia: Clinical Evidence and Mechanistic Insights.

BACKGROUND AND AIMS: Helicobacter pylori is a persistent gastric microbe with systemic consequences beyond the stomach, yet its contribution to host lipid dysregulation remains unclear.

METHODS

We analyzed clinical data from 57,295 adults with documented H. pylori status and detailed lipid profiles, including the non-HDL-C to HDL-C ratio (NHHR). Mechanistic validation was performed using in vitro and in vivo H. pylori PMSS1 infection models, combined with single-cell RNA sequencing, molecular analyses, histopathology, and lipidomics.

RESULTS

Helicobacter pylori infection was associated with increased LDL cholesterol and triglycerides, reduced HDL cholesterol, and elevated NHHR, which independently predicted hyperlipidemia risk. At the mechanistic level, H. pylori infection consistently suppressed gastric expression of Gpihbp1, a key mediator of lipoprotein lipase-dependent lipid transport. Infected mice developed systemic hyperlipidemia and exhibited lipidomic remodeling characterized by glycerolipid accumulation and reduced phosphatidylcholine species. Importantly, genetic deficiency of Gpihbp1 promoted gastric H. pylori colonization and exacerbated mucosal inflammation, revealing a reciprocal interaction between host lipid metabolism and bacterial persistence.

CONCLUSION

These findings define a microbiota-host lipid transport axis linking chronic H. pylori infection to dyslipidemia and suggest that integrated targeting of microbial infection and metabolic dysfunction may offer therapeutic benefit.