The Gram-negative microaerophilic bacterium Helicobacter pylori (H. pylori, Hp) colonizes the human gastric mucosa and forms a chronic infection closely associated with atrophic gastritis, peptic ulcer and gastric cancer and is considered to be one of the most prevalent chronic bacterial infections worldwide (1, 2), affecting nearly half of the world’s population and 35.6% of Americans. Although H. pylori infection has decreased in recent decades, it continues to be an important burden of global health given its close association to a range of other diseases (3). Helicobacter pylori is listed as the category I carcinogen by the World Health Organization, and is a major factor in the pathogenesis of chronic gastritis, peptic ulcer disease, and noncardiac gastric cancer. Over 75% of duodenal ulcer cases and 17% of gastric ulcer cases are related to infection. In addition, it has been associated with extra-gastrointestinal diseases, including iron deficiency anemia, idiopathic thrombocytopenic purpura (4), cardiovascular disease (5), endocrine dysfunction (6), and Alzheimer’s disease (7). The health burden associated with H. pylori infection extends beyond its direct clinical manifestations, affecting patients’ quality of life and imposing considerable healthcare costs due to prolonged treatment and disease management.

Previous studies have shown that H. pylori infection is often accompanied by changes in some metabolic indicators and lipid profiles in the blood, for example, a study of black urban Congolese individuals indicate that H. pylori infection leads to a significant increase in SUA (8, 9), and another study of adults from Australia and New Zealand indicate that chronic Hp infection reduces the level of HDL in plasma (2, 10). Serum uric acid (SUA) is widely recognized as a biomarker for measuring abnormal renal metabolic function (10). When the concentration of serum uric acid (SUA) increases, it often indicates the occurrence of cell damage (11), and it is closely linked to various disease states such as gout (12), dyslipidemia and cardiovascular disease (13). In contrast, normal high-density lipoprotein cholesterol (HDL) plays an important role in cardiovascular health and overall protection, by promoting reverse transport of cholesterol, as well as having significant anti-inflammatory, antioxidant, and anti-thrombotic capacity (14). Notably, the SUA-to-HDL ratio (UHR) has emerged as a novel biomarker reflecting both inflammatory and metabolic states. Recent studies have demonstrated that UHR is superior to individual SUA or HDL levels in predicting a wide spectrum of diseases, including diabetic nephropathy (15), non-alcoholic fatty liver disease (16), hypertension, thyroid inflammation and other diseases (17). However, its relationship with H. pylori infection remains underexplored. This study aims to investigate the association between UHR and H. pylori infection, using a large, nationally representative dataset to provide insights into its potential role as a clinical biomarker in this context.

This study is among the first to explore the association between the SUA-to-HDL ratio (UHR) and H. pylori infection, revealing a significant positive correlation that persists after adjusting for multiple demographic, metabolic, and inflammatory confounders. These findings highlight the potential of UHR as a novel biomarker reflecting the interplay between metabolic dysregulation and chronic infection. While prior research has independently linked elevated SUA and reduced HDL to inflammation and metabolic dysfunction, our results underscore the clinical utility of UHR as a composite index that integrates these factors.

The data of this study showed that the high quartile UHR individuals were more male, smokers, drinkers and hypertensive diabetic patients, and had lower HEI levels and higher TG, BUN and SCR levels, which were consistent with the results of previous studies to varying degrees (16, 20). In the association between UHR and Hp infection, we found that UHR was positively correlated with Hp infection regardless of model adjustment. After adjusting for multiple confounders, the risk of Hp infection increased by 15% for each SD increase in UHR. (21) Furthermore, subgroup analyses indicate that this relationship is robust across diverse demographic and clinical subpopulations, suggesting its generalizability and relevance to clinical practice. The marginal interaction observed in the diabetes subgroup, while intriguing, requires further investigation to clarify its biological significance.

The observed association between UHR and H. pylori infection may reflect underlying pathophysiological mechanisms shared by metabolic and inflammatory processes (22). Elevated SUA, a byproduct of purine metabolism, is known to promote oxidative stress and low-grade systemic inflammation, both of which can facilitate (23–25). H. pylori colonization and persistence in the gastric mucosa (26). Moreover, reduced HDL levels impair cholesterol transport and endothelial protection, which may compromise the host’s immune defense against bacterial infection (27–29). Together, these metabolic alterations may create a permissive environment for H. pylori to establish chronic infection, contributing to the observed association. Besides, for the interaction observed in the diabetes subgroup, we hypothesized that this may be due to increased levels of inflammation and metabolic disorders in diabetic patients themselves, which in turn disrupt the normal metabolic pathways of SUA and HDL in humans (30), thus reducing the negative effect of UHR. (23, 31)

The implications of these findings extend beyond H. pylori infection, given the established role of UHR in predicting cardiovascular and metabolic diseases. The overlap between metabolic and infectious pathways emphasizes the importance of a multidisciplinary approach to disease prevention and management. For instance, targeting UHR through dietary and pharmacological interventions may not only improve metabolic health but also mitigate the risk of chronic infections, including H. pylori. This hypothesis warrants exploration in future interventional studies.

The study has several limitations. First, this cross-sectional study was unable to establish a causal relationship between serum UHR levels and Hp infection, and the absence of follow-up data limits understanding of how UHR changes with Hp treatment or progression. Besides, our study does not explore the biological mechanisms underlying the association between UHR and Hp infection, which needs further investigation. Moreover, despite adjustments, residual confounding factors, such as dietary habits, physical activity, or genetic predisposition, may influence the results. Finally, because the NHANES database represents only the U.S. population, the results may have some limitations worldwide. To further confirm our conclusions, a prospective cohort study with a larger sample size is needed.

In conclusion, our study identifies UHR as a promising biomarker for H. pylori infection, reflecting its potential role at the intersection of metabolic dysfunction and chronic inflammation. Future research should focus on elucidating the mechanistic underpinnings of this relationship, exploring its clinical utility in risk stratification and targeted interventions, and validating these findings in diverse populations. By integrating metabolic and infectious pathways, UHR offers a novel perspective on the complex interplay between chronic diseases, advancing our understanding of their shared pathophysiology.