TO THE EDITOR
We read with great interest the research by Ye et al[1], in which the authors concurrently investigated the associations between Helicobacter pylori (H. pylori) infection and various metabolic indicators, including obesity, glucose, lipids, blood pressure, and metabolic dysfunction-associated steatotic liver disease (MASLD) in 28624 Chinese adults. Their research indicated that H. pylori infection correlates with advanced age and exhibits a U-shaped relationship with body mass index (BMI). The findings demonstrated that elevated glucose, diastolic blood pressure, and obesity levels constitute independent risk factors for H. pylori infection (odds ratio = 1.003-1.079), whereas elevated high-density lipoprotein levels provide protection (odds ratio = 0.837). These results indicate a dual role of H. pylori infection in promoting metabolic disturbances and MASLD progression. The association between H. pylori infection and metabolic parameters, like bilirubin and cholesterol, has been reported[2]. Multiple studies, including meta-analysis and retrospective investigations confirm a positive correlation between H. pylori infection and MASLD prevalence[3-6]. This association remains consistent across demographics and ethnicities, as evidenced by large multicenter studies in American, Asian, and Hispanic populations[7,8].
In this study, the author employed BMI, a standard clinical measurement, to assess body fat in participants ranging from 18 to over 70 years of age. Although BMI is a general body fat indicator, it fails to account for variations in muscle mass and bone density, which change markedly with age progression. Direct measurement of body fat percentage or imaging modalities including magnetic resonance imaging and dual-energy X-ray absorptiometry, would bring more accurate data for investigating the relationship between obesity and H. pylori infection in a study population with such a broad age spectrum. Regarding H. pylori positivity and MASLD detection rates across age groups, the data revealed that the 50 years old to 69 years old cohort demonstrated the highest H. pylori positivity, while MASLD detection rates were actually higher in the 30 years old to 49 years old group [36.1% (4345/12047)] and people aged 70 and above [36.7% (659/1798)], compared to the 50 years old to 69 years old group [36.0% (4354/12078)]. These differences in MASLD detection rates achieved statistical significance (χ2 = 431.65, P < 0.05). This disparity indicates an inconsistency between H. pylori positivity and MASLD detection rates. Additionally, the disproportionate increase in H. pylori positivity relative to MASLD detection rates suggests that H. pylori may have a limited impact on MASLD development, with other factors potentially exerting stronger influences. Potential confounding variables include socioeconomic status, dietary factors, and comorbidities such as cardiovascular diseases, chronic inflammatory conditions and hormonal changes[9-13]. These factors are likely to vary with age and may influence the development of MASLD across different age groups.
The results demonstrated that higher blood glucose, diastolic blood pressure, and BMI constitute hazard elements for the infection of H. pylori, while elevated high-density lipoprotein levels function as a phylactic issue towards the infection of H. pylori. MASLD represents one of the most prevalent liver disorders worldwide, stemming from underlying metabolic conditions, including overweight/obesity, insulin resistance, and metabolic dysfunction[9-11]. This study suggested that H. pylori infection contributes to MASLD progression by functioning as an independent risk factor that promotes dyslipidemia and insulin resistance. The findings indicated that although total cholesterol concentration in the H. pylori-positive group exceeded that of the negative control group by 0.05 mmol/L (P < 0.05), the clinical significance remained limited and may not necessitate intervention, given that the clinical intervention threshold for total cholesterol typically stands at ≥ 5.2 mmol/L, with mean total cholesterol levels in both groups falling below this threshold (4.8 mmol/L vs 4.75 mmol/L). Similarly, while the differences in systolic and diastolic blood pressures between the H. pylori-positive and H. pylori-negative groups showed statistical significance (2.1 mmHg and 1.3 mmHg, respectively) but their clinical relevance remained modest unless interpreted according to individual baseline contexts. Regarding blood glucose, the mean values for the H. pylori-positive group and the H. pylori-negative group were 5.43 and 5.27 mmol/L respectively, neither meeting the prediabetes threshold of > 5.6 mmol/L.
Although this study demonstrated associations between H. pylori, metabolic dysfunction and MASLD, it does not establish a causal relationship between H. pylori infection and MASLD development. Future investigations should utilize prospective cohort studies to evaluate objectively the influence of H. pylori infection on the development of insulin resistance, dyslipidemia and MASLD longitudinally. This could help evaluate if the aforementioned minor variations will increase, decrease or remain relatively unchanged over time, and if they will become clinically significant to the point of warranting clinical intervention. Future research should also investigate the effect of H. pylori eradication on these variations, whether they will persist or disappear. Mechanistic studies should be conducted to explore the role of H. pylori on metabolic diseases. The currently prevailing theory suggests that persistent H. pylori infection triggers an inflammatory response by continuously damaging the gastric lining, resulting in the sequential stimulation of both innate and adaptive immune mechanisms. Gastric inflammation may propagate systemically through circulating inflammatory mediators thereby promoting sustained low-intensity inflammatory states, a characteristic feature observed in H. pylori-related diseases beyond the gastroduodenal region[13]. Studies have shown that H. pylori infection could trigger an increase in specific biomarkers such as tumor necrosis factor-α, interleukin (IL)-1β, IL-10, IL-8, IL-17, and IL-6. They are cytokines associated with destruction of pancreatic β cells, insulin resistance, obesity and metabolic syndrome[12]. Further studies could explore the role of these cytokines in the mechanism through which H. pylori causes metabolic diseases. Other mechanistic pathways such as oxidative stress, hormonal and gut hormone disruption, as well as gut microbiota dysbiosis should also be investigated[12,13]. Studies should evaluate how these pathways collectively or independently affect insulin resistance, dyslipidemia and MASLD. This will help establish a causative relation between H. pylori and metabolic disorders. This study made a valuable contribution to the fields of hepatology and gastroenterology by illuminating the extragastric effects of H. pylori infection on metabolic diseases. The research establishes a foundation for future investigations into the relationships between H. pylori infection, metabolic disorders, and MASLD.
