Helicobacter pylori infection is linked to metabolic dysfunction and associated steatotic liver disease: A large cross-sectional study

Abstract

BACKGROUND

Helicobacter pylori (H. pylori), a globally widespread pathogen affecting half of the global population, has been increasingly implicated in metabolic disorders, including obesity, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is a common condition, impacting nearly one in four adults globally. It also shares significant pathophysiological links with metabolic syndrome. Despite the fact that mechanistic hypotheses (such as oxidative stress and inflammation) have been proposed to explain these relationships, large-scale studies comprehensively assessing multifactorial metabolic associations are lacking. We proposed that H. pylori infection may independently correlate with unfavorable metabolic profiles and the presence of MASLD among adults in a large cohort.

AIM

To investigate the associations of H. pylori infection with obesity, glucose, lipids, blood pressure, and MASLD in Chinese adults.

METHODS

This study included 28624 adults recruited from the Physical Examination Center at Nanchang University's Second Affiliated Hospital. The 13C-urea breath test was used to identify H. pylori infection, while abdominal ultrasound was employed for MASLD diagnosis. The relationships between H. pylori infection and metabolic factors were analyzed via multivariate logistic regression.

RESULTS

The overall H. pylori infection incidence was 26.8%, with higher rates observed in older adults (≥ 70 years: 26.1% vs 18-29 years: 24.6%, P < 0.001) and obese individuals [body mass index (BMI) ≥ 28 kg/m²: 30.0% vs normal BMI: 25.3%, P < 0.001]. H. pylori-positive individuals exhibited elevated blood glucose (5.43 ± 1.55 mmol/L vs 5.27 ± 1.23 mmol/L, P < 0.001), low-density lipoprotein cholesterol (2.97 ± 0.76 mmol/L vs 2.94 ± 0.75 mmol/L, P < 0.001), and blood pressure (systolic: 123.49 ± 19.06 mmHg vs 122.85 ± 18.33 mmHg, P = 0.009; diastolic: 75.48 ± 12.37 vs 74.9 mmHg ± 11.9 mmHg, P < 0.001) levels. Among MASLD patients, infection was associated with increased glucose (5.82 ± 1.95 mmol/L vs 5.60 ± 1.60 mmol/L, P < 0.001), total cholesterol (5.05 ± 1.03 mmol/L vs 5.00 ± 1.00 mmol/L, P = 0.039), BMI (26.23 ± 3.00 kg/m² vs 26.04 ± 2.96 kg/m², P = 0.004), and blood pressure (systolic: 129.5 ± 20.00 mmHg vs 128.49 ± 17.62 mmHg, P = 0.009; diastolic: 79.87 ± 12.07 mmHg vs 79.04 ± 11.76 mmHg, P = 0.002) levels. Multivariate analysis demonstrated elevated glucose [odds ratio (OR) = 1.079, P < 0.001], BMI (OR = 1.016, P = 0.002), and diastolic pressure (OR = 1.003, P = 0.048) levels as independent risk factors, with high-density lipoprotein (HDL) being observed as a protective factor (OR = 0.837, P < 0.001).

CONCLUSION

H. pylori infection correlates with older age, obesity, elevated glucose levels, and elevated diastolic blood pressure, whereas HDL protects against H. pylori infection, thus underscoring its role in metabolic disturbances and MASLD.

Key Words: Helicobacter pylori; Obesity; Blood glucose; Lipid profile; Blood pressure; Metabolic dysfunction-associated steatotic liver disease

Core Tip: This large cross-sectional study involving 28624 adults revealed that Helicobacter pylori (H. pylori) infection is correlated with metabolic disturbances, particularly in obese and older individuals. H. pylori-positive individuals exhibited elevated blood glucose, low-density lipoprotein cholesterol, and blood pressure levels, with worse metabolic profiles being observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). High blood glucose, body mass index, and diastolic pressure levels were identified as significant risk factors for H. pylori infection, whereas high-density lipoprotein was observed to be a protective factor. These findings suggest that H. pylori infection may contribute to metabolic disorders and MASLD progression, thereby offering insights for future research and prevention strategies.

INTRODUCTION

Helicobacter pylori (H. pylori), a gram-negative bacterium, predominantly inhabits the gastric mucosa and is strongly linked to various gastric disorders, including gastritis, peptic ulcers, and gastric cancer[1]. H. pylori exhibits a remarkably high rate of global infection, impacting nearly half of the world's population[2], and this prevalence is particularly elevated in developing nations[3]. However, emerging research indicates that H. pylori infection could potentially be associated with a range of metabolic disturbances, including obesity, impaired glucose metabolism, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD)[4-8].

MASLD poses a significant health challenge, impacting a substantial portion of the global populace[9,10]. It is closely related to metabolic syndrome, obesity, and insulin resistance, and with its incidence escalating concurrently with the rise in these associated conditions[11-13]. Recent investigations have underscored the involvement of H. pylori infection in the onset and advancement of MASLD, potentially through pathways like heightened oxidative stress, widespread inflammation, and changes in lipid metabolism[14,15].

Despite these advances, significant gaps remain in the literature concerning H. pylori and metabolic disorders. First, the link between H. pylori infection and metabolic disorders (especially MASLD) is still variably shown across studies, with some studies indicating positive correlations[16] and others noting no substantial associations[17]. These discrepancies may stem from variations in study design, population characteristics, and sample sizes. Second, most of the studies to date have focused on individual metabolic parameters [such as body mass index (BMI) and blood glucose] rather than on the comprehensive evaluation of multiple metabolic factors within the same population. Third, few large-scale epidemiological studies have been conducted that can provide robust evidence examining the link between H. pylori infection and metabolic health factors, especially across varied populations.

In this context, this study was formulated as a large-scale, cross-sectional examination involving over 28000 adults undergoing routine health examinations. By concurrently assessing the links between H. pylori infection and various metabolic indicators (such as obesity, blood glucose, lipid profiles, blood pressure, and MASLD), we aimed to offer a more in-depth insight into the possible involvement of H. pylori in metabolic disorders. The large sample size of this study boosts the statistical robustness and broader applicability of our results, whereas the use of standardized diagnostic criteria ensures reliability.

MATERIALS AND METHODS

Study participants

This is a large-scale cross-sectional study. The selected participants included individuals who underwent 13C-urea breath tests and abdominal ultrasonography at the Health Check-up Center of the Second Affiliated Hospital of Nanchang University between January 2023 and December 2023. Participants had complete demographic and clinical data, including gender, age, BMI, blood pressure (systolic and diastolic), lipid profiles [total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL)], and fasting glucose. The exclusion criteria were as follows: (1) Age below 18 years; (2) Fatty liver caused by non-nonalcoholic factors, such as viral hepatitis, alcohol use, or drug-induced injury; (3) Heavy alcohol intake in the past two years (> 21 drinks/week for men, > 14 drinks/week for women); and (4) History of cancer, gastrectomy, or severe liver/kidney dysfunction. The study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University, with informed consent waived.

Detection and diagnosis of H. pylori

The participants were required to fast or abstain from food and water for at least four hours prior to the examinations. The 13C-urea breath test was conducted via a commercially available kit, with the procedure performed by trained medical personnel. after which they placed the breath tube at the base of a sample vial and gently exhaled into it for 4-5 seconds. The breath tube was subsequently removed, and the vial was immediately sealed; this constituted the 0-minute breath sample. After ingesting a 13C-urea tablet with 80-100 mL of cool drinking water, the participants were asked to sit quietly. Twenty minutes later, a breath sample was collected via the same previously described method. Both the 0-minute and 20-minute breath samples were analyzed via the appropriate equipment. In accordance with the current research consensus, a positive result in the 13C-urea breath test signals an active H. pylori infection[18,19].

MASLD examination and diagnosis

Participants had to fast for 10-12 hours before the examinations. Ultrasonography was conducted by a sonographer who was also a chief physician (or held a higher qualification), using a Philips (Italy) PHILIP-SIU22 high-resolution multifunctional color Doppler ultrasound diagnostic device. A report was generated after the abdominal ultrasound[20]: (1) Documentation of hepatic steatosis via imaging or histological methods; (2) Minimal alcohol consumption (not exceeding 21 standard drinks weekly for men or 14 standard drinks weekly for women); (3) Absence of alternative causes for hepatic steatosis; and (4) No concurrent conditions leading to chronic liver disease, such as hepatitis C, drug-induced liver injury, parenteral nutrition, Wilson’s disease, or severe malnutrition.

Anthropometric and biochemical assessments

The participants were instructed to minimize the intake of high-fat and high-calorie foods three days prior to the examinations. After a fasting period exceeding 12 hours, participants' height, weight, and blood pressure (both systolic and diastolic) were measured by trained personnel using standardized equipment. The BMI was computed by dividing the weight in kilograms by the square of the height in meters (kg/m²). Venous blood samples were drawn from the antecubital fossa of the participants, and levels of total cholesterol, triglycerides, LDL, HDL, and fasting blood glucose were assessed via an automated biochemical analyzer.

RESULTS

Comparison of data between the H. pylori-positive and H. pylori-negative groups

Among the 28624 individuals who underwent the 13C-urea breath test at the Physical Examination Center of the Second Affiliated Hospital of Nanchang University from January 2023 to December 2023 and who met the inclusion and exclusion criteria, 7678 individuals were positive for H. pylori infection, with a positive rate of 26.8% being observed (7678/28624). Participants were divided into two groups according to their H. pylori infection status: The H. pylori-positive group (n = 7678) and the H. pylori-negative group (n = 20946). Clinical data comparison revealed that the H. pylori-positive group exhibited significantly older ages, as well as greater blood glucose, total cholesterol, LDL, BMI, and systolic and diastolic blood pressure levels, along with greater MASLD detection rates, than the H. pylori-negative group, whereas the levels of HDL were considerably lower in the H. pylori-positive group. The differences reached statistical significance (P < 0.05). No significant differences were found in triglyceride levels or sex distributions between the two groups, with P values exceeding 0.05 (Table 1).

Table 1 Comparison of clinical data between Helicobacter pylori-positive and Helicobacter pylori-negative groups.

Parameter	H. pylori-negative group (n = 20946)	H. pylori-positive group (n = 7678)	t value	P value
Age (years)	46 ± 14.86	46.43 ± 14.45	2.443	0.015
Blood glucose (mmol/L)	5.27 ± 1.23	5.43 ± 1.55	-7.79	0.001
HDL (mmol/L)	1.41 ± 0.37	1.38 ± 0.37	4.23	0.001
Total cholesterol (mmol/L)	4.85 ± 0.97	4.88 ± 0.99	-2.37	0.018
Triglycerides (mmol/L)	1.62 ± 1.48	1.65 ± 1.48	-1.61	0.107
LDL (mmol/L)	2.94 ± 0.75	2.97 ± 0.76	-3.2	0.001
BMI (kg/m²)	23.64 ± 3.35	23.89 ± 3.46	-5.3	0.001
Systolic blood pressure (mmHg)	122.85 ± 18.33	123.49 ± 19.06	-2.57	0.009
Diastolic blood pressure (mmHg)	74.9 ± 11.9	75.48 ± 12.37	-3.53	0.001
Gender (male/female)	11803/9143	4258/3420	χ2 = 1.821	0.179
MASLD detection rate	7424/13522	2845/4833	χ2 = 6.331	0.012

¹The test method for this item is the χ² test.

Data are presented as mean ± SD or n (%). Continuous variables were analyzed via the Student’s t-test; categorical variables were analyzed via the χ² test. H. pylori: Helicobacter pylori; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; BMI: Body mass index; MASLD: Metabolic dysfunction-associated steatotic liver disease.

Comparison of clinical data between the H. pylori-positive and H. pylori-negative groups within the MASLD cohort

Within the cohort of MASLD patients, individuals with H. pylori infection had significantly higher blood glucose, total cholesterol, BMI, systolic blood pressure (SBP), and diastolic blood pressure compared to those without H. pylori infection (P < 0.05). However, no significant differences were found between the two groups with respect to age, HDL levels, triglyceride levels, LDL levels, or sex (P > 0.05; Table 2).

Table 2 Comparison of clinical data between Helicobacter pylori-positive and Helicobacter pylori-negative groups within the metabolic dysfunction-associated steatotic liver disease cohort.

Parameter	H. pylori-negative group (n = 7424)	H. pylori-positive group (n = 2845)	t value	P value
Age (year)	48.39 ± 13.77	48.91 ± 13.19	-1.76	0.79
Blood glucose	5.60 ± 1.60	5.82 ± 1.95	-5.3	0.001
HDL (mmol/L)	1.23 ± 0.30	1.22 ± 0.30	1.31	0.191
Total cholesterol (mmol/L)	5.00 ± 1.00	5.05 ± 1.03	-2.07	0.039
Triglycerides (mmol/L)	2.27 ± 1.99	2.30 ± 1.91	-0.404	0.686
LDL (mmol/L)	3.13 ± 0.75	3.16 ± 0.76	-1.78	0.076
BMI (kg/m²)	26.04 ± 2.96	26.23 ± 3.00	-2.88	0.004
Systolic blood pressure (mmHg)	128.49 ± 17.62	129.5 ± 20.00	-2.6	0.009
Diastolic blood pressure (mmHg)	79.04 ± 11.76	79.87 ± 12.07	-3.16	0.002
Gender (male/female)	5538/1886	2075/770	χ2 = 2.9591	0.85

¹The test method for this item is the χ² test.

Data are presented as the mean ± SD or n (%). Continuous variables were analyzed via the Student’s t-test; categorical variables were analyzed via the χ² test. H. pylori: Helicobacter pylori; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; BMI: Body mass index.

Comparison of H. pylori positivity and MASLD detection rates across different age groups

The participants were grouped according to the following age brackets: 18-29 years (4501 cases), 30-49 years (12047 cases), 50-69 years (10278 cases), and 70 years and above (1798 cases). The H. pylori positivity rates were 24.6% (1106/4501) for the 18-29-year-old group, 26.9% (3241/12047) for the 30-49-year-old group, 27.8% (2862/10278) for the 50-69-year-old group, and 26.1% (469/1798) for those individuals aged 70 years and above. The differences in H. pylori positivity rates across the age groups were statistically significant (χ² = 34.661, P < 0.05; Table 3 and Supplementary Figure 1). The MASLD detection rates were 20.2% (911/4501) for the 18-29-year-old group, 36.1% (4345/12047) for the 30-49-year-old group, 36.0% (4354/12078) for the 50-69-year-old group, and 36.7% (659/1798) for those individuals aged 70 years and above. The differences in MASLD detection rates across the age groups were also statistically significant (χ² = 431.65, P < 0.05; Table 4 and Supplementary Figure 2). The 50-69-year-old group exhibited the highest H. pylori positivity and MASLD detection rates, whereas the 18-29-year-old group exhibited the lowest rates. The trends of H. pylori positivity and MASLD detection rates were consistent with the trends of age.

Table 3 Age-stratified prevalence of Helicobacter pylori infection and statistical comparisons.

Age group	Number of cases	H. pylori-positive cases	H. pylori-positivity rate (%)	χ2	P value
18-29	4501	1106	24.6	34.661	0.001
30-49	12047	3241	26.9
50-69	12078	2862	23.7
≥ 70	1798	469	26.1

The χ² trend test was used to evaluate age-related trends in infection rates. H. pylori: Helicobacter pylori.

Table 4 Age-stratified prevalence of metabolic dysfunction-associated steatotic liver disease.

Age group	Number of cases	MASLD cases	MASLD detection rate (%)	χ2	P value
18-29	4501	911	20.2	431.65	0.001
30-49	12047	4345	36.1
50-69	12078	4354	36.0
≥ 70	1798	659	36.7

The χ² trend test was used to assess age-related trends. MASLD: Metabolic dysfunction-associated steatotic liver disease.

Comparison of H. pylori infection rates among different body types

According to the criteria of the Chinese Obesity Task Force (17), the 28624 participants were divided into four categories according to their BMI: The underweight group (BMI < 18 kg/m²) with 805 cases, the normal weight group (18 ≤ BMI < 24) with 15150 cases, the overweight group (24 ≤ BMI < 28) with 9759 cases, and the obese group (BMI ≥ 28) with 2910 cases. The H. pylori positivity rates were 29.4% (237/805) for the underweight group, 25.3% (3826/15150) for the normal weight group, 28.1% (2743/9759) for the overweight group, and 30.0% (872/2910) for the obese group (Table 5 and Figure 1).

Figure 1 Associations between Helicobacter pylori infection and body mass index . The χ² test revealed significant differences in Helicobacter pylori infection rates across body mass index (BMI) groups [χ² (3) = 44.65, P < 0.001]. Cramer’s V = 0.04 (95%CI: 0.02-0.05) suggested a weak association. The Bayesian factor [log(BF₀₁) = −10.08] strongly supported the alternative hypothesis. BMI categories: < 18 kg/m² (underweight), 18-23.9 kg/m² (normal weight), 24-27.9 kg/m² (overweight), ≥ 28 kg/m² (obese). Hp: Helicobacter pylori.

Table 5 Body mass index-stratified prevalence of Helicobacter pylori infection and statistical comparisons.

BMI	Number of cases	H. pylori positive cases	H. pylori positivity rate (%)	χ2	P value
< 18	805	237	29.4%	44.654	0.001
18 ≤ BMI < 24	15150	3826	25.3%
24 ≤ BMI < 28	9759	2743	28.1%
≥ 28	2910	872	30.0%

The χ² trend test was used to evaluate body mass index-related trends. BMI: Body mass index; H. pylori: Helicobacter pylori.

Analysis of risk factors for H. pylori infection

Variables showing significance in the preliminary univariate analysis, such as age, blood glucose levels, HDL, total serum cholesterol, LDL, BMI, systolic and diastolic blood pressure, and MASLD (Table 1 and Figure 2), were incorporated into the binary logistic regression analysis. The presence or absence of H. pylori infection was set as the dependent variable (0 for absence, 1 for presence). The analysis revealed that elevated blood glucose, BMI, and diastolic blood pressure are risk factors for H. pylori infection, while a higher HDL level serves as a protective factor against H. pylori infection (Table 6).

Figure 2 Binary logistic regression analysis of risk factors for Helicobacter pylori infection. The figure presents the results of a binary logistic regression analysis to assess risk factors associated with Helicobacter pylori infection. The "odds ratio" column displays the odds ratio for each variable, with different colors distinguishing protective factors from risk factors. BMI: Body mass index; HDL: High-density lipoprotein; LDL: Low density lipoprotein; NAFLD: Non-alcoholic fatty liver disease.

Table 6 Multivariable logistic regression analysis of risk factors for Helicobacter pylori infection.

Variable	β	β SE	Wald	P value	OR	95%CI
Age	0.001	0.001	0.254	0.614	1.001	0.998-1.003
Blood glucose	0.76	0.01	57.568	0.001	1.079	1.058-1.100
HDL	-0.178	0.055	10.403	0.001	0.837	0.751-0.932
Total cholesterol	0.075	0.042	3.195	0.074	1.077	0.993-1.169
LDL	-0.041	0.049	0.694	0.405	0.96	0.871-1.057
BMI	0.016	0.005	9.816	0.002	1.016	1.006-1.026
Systolic blood pressure	-0.002	0.001	2.748	0.097	0.998	0.996-1.000
Diastolic blood pressure	0.003	0.002	3.991	0.048	1.003	1.000-1.007
MASLD	-0.058	0.034	2.858	0.091	0.944	0.883-1.009

Notably, higher blood glucose [odds ratio (OR) = 1.079], body mass index (OR = 1.016), and diastolic blood pressure (OR = 1.003) levels were independent risk factors for Helicobacter pylori infection, whereas elevated high-density lipoprotein (OR = 0.837) levels had a protective effect. Metabolic dysfunction-associated steatotic liver disease was not significantly associated with infection risk (P = 0.091). OR: Odds ratio; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; BMI: Body mass index; MASLD: Metabolic dysfunction-associated steatotic liver disease.

DISCUSSION

In the research, the prevalence of H. pylori infection among the health examination population was 26.82%. The incidence rate is lower than the 50% reported in China's general population[21]. The lower H. pylori infection rate seen in this study may be due to the inclusion of individuals who had previously received H. pylori eradication treatment, the rapid development of Chinese society, improvements in the dietary habits of Chinese residents, and a stronger health protection awareness among the health examination population.

This study revealed that both the H. pylori positivity rate and the detection rate of MASLD were greater in the ≥ 70 years group than in the other age groups, whereas the 18-29 years age group exhibited the lowest rates of both H. pylori positivity and MASLD detection. The similar trends of associations of H. pylori positivity and MASLD detection rates with age suggest a correlation between H. pylori infection and the occurrence of MASLD. The rise in H. pylori infection prevalence among older adults could be attributed to age-related physiological changes, including decreased gastric acid and prostaglandin production, delayed gastric emptying, and compromised gastric mucosal defense mechanisms[22,23].

The relationship between H. pylori infection and overweight or obesity shows regional variability, as research results remain inconsistent. The majority of studies in Asian countries have shown a positive relationship between H. pylori infection and overweight/obesity[24,25]. In contrast, research from European and American countries has often demonstrated no correlation between H. pylori infection and overweight/obesity[26]. This study revealed that the H. pylori infection rate is the lowest among individuals with a normal BMI, and it progressively increases with increasing BMI. Notably, our study revealed a greater prevalence of H. pylori infection in the underweight group than in the normal weight group, which contrasts with the "positive association between obesity and infection" pattern reported in most Asian studies[24,25]. We hypothesize that this discrepancy might be associated with the distinct features of the Chinese health examination population, including the observation that underweight individuals may experience malnutrition or gastrointestinal symptoms, thereby potentially increasing their susceptibility to H. pylori infection. This finding suggests that the metabolic impacts of H. pylori infection may exhibit population heterogeneity, thus warranting further validation in broader populations.

MASLD ranks among the most common liver disorders globally and stems from underlying metabolic issues, including overweight/obesity, type 2 diabetes, and metabolic dysfunction. The association between H. pylori infection and MASLD was initially suggested when H. pylori 16S rDNA was detected in liver biopsy samples from MASLD patients[27]. Numerous studies[28-31] have indicated that the following mechanisms may explain how H. pylori influences MASLD: (1) H. pylori infection increases the permeability of the gastrointestinal epithelium, thereby facilitating the translocation of the gut microbiota and its metabolites into the portal circulation, activating inflammation in hepatocytes, and ultimately promoting the progression of MASLD; (2) Certain vasoactive and proinflammatory substances, such as interleukins, TNF-α, interferon-γ, eicosanoids, and acute-phase proteins , may be released and contribute to the development of metabolic syndrome and MASLD; and (3) H. pylori-induced oxidative stress, coupled with atrophic gastritis associated with vitamin B12 and folate deficiency, apoptosis, and reduced adiponectin levels, may represent additional pathological connections between H. pylori infection and MASLD. The results indicate that H. pylori infection might be involved in the development and progression of MASLD through multiple pathways, thus emphasizing the necessity for additional research to clarify these interactions and their clinical significance.

Compared with previous studies, this study represents a pioneering effort to concurrently examine the relationships between H. pylori infection and a range of metabolic indicators, such as blood glucose, lipid profiles, blood pressure, BMI, and MASLD, in a health examination population exceeding 28000 individuals. This large-scale cross-sectional design offers a more comprehensive investigation of the precise relationship between H. pylori infection and metabolic disorders, revealing that the H. pylori-positive group had significantly higher levels of blood glucose, triglycerides, total cholesterol, LDL, BMI, SBP, diastolic blood pressure, as well as greater ages and MASLD detection rates, compared to the H. pylori-negative group, while HDL levels were lower. Although the total cholesterol concentration in the H. pylori-positive group was significantly higher than that in the negative control group, with a difference of 0.05 mmol/L (P < 0.05), the clinical significance of this difference may be limited. According to relevant studies, the clinical intervention threshold for total cholesterol is typically ≥ 5.2 mmol/L, and the mean total cholesterol levels in both groups in this study were observed to be below this threshold (positive group: 4.8 mmol/L vs negative group: 4.75 mmol/L). Therefore, this difference may reflect a significant association between the groups rather than a direct need for clinical intervention. Similarly, the mean systolic and diastolic blood pressures in the H. pylori-positive group were 2.1 mmHg and 1.3 mmHg greater than those in the H. pylori-negative group, respectively. Although these differences were statistically significant, their clinical relevance should be interpreted in the context of individual baseline blood pressure levels. For example, in individuals with normal blood pressure, such minor differences may not warrant therapeutic intervention. However, in populations with prehypertension or obesity, these findings may suggest that H. pylori infection acts as a synergistic risk factor for metabolic disturbances.

In the MASLD cohort, individuals infected with H. pylori exhibited elevated blood glucose, cholesterol levels, BMI, and blood pressure (both systolic and diastolic) compared to those without H. pylori infection. Multivariate binary logistic regression analysis indicated that high blood glucose, high BMI, and high diastolic blood pressure levels are risk factors for H. pylori infection, whereas HDL is a protective factor against H. pylori infection. Based on the results of our study, H. pylori infection may lead to lipid metabolism disorders, increase insulin resistance, and ultimately contribute to the onset of MASLD via the impact of this infection on blood lipid and glucose levels. However, the evidence linking H. pylori infection and MASLD remains limited, with conflicting findings being observed in domestic and international studies; moreover, there is a lack of sufficient large-sample retrospective studies and multicenter prospective studies. These findings support the existence of an interaction between H. pylori infection and metabolic abnormalities. In addition to the well-established mechanisms of inflammation and oxidative stress, we propose that H. pylori infection may influence metabolic health through the gut microbiota-liver axis. Recent studies have suggested that H. pylori infection can alter the gastric pH, thereby affecting the gut microbiota composition (such as by increasing the Bacteroidetes/Firmicutes ratio)[32]. Such microbiota dysbiosis may exacerbate hepatic lipid deposition via pathways involving short-chain fatty acid metabolism and bile acid transformation. Future research should employ metagenomics and metabolomics technologies to directly validate the impacts of H. pylori infection on the gut-liver metabolic network.

Based on the results of this study, we recommend incorporating H. pylori screening into the routine health management of the following high-risk groups: (1) The elderly population (≥ 70 years), in which the infection rate of this population is significantly increased, with a higher coexistence risk of MASLD being observed; (2) Patients with obesity or metabolic syndrome, wherein infection may exacerbate insulin resistance and dyslipidemia; and (3) Individuals with unexplained weight loss, in which infection may be associated with impaired digestion and absorption. For these groups, H. pylori eradication therapy may not only improve gastrointestinal health but also indirectly ameliorate metabolic status by reducing chronic inflammation and oxidative stress. In clinical practice, metabolic indicators (such as blood glucose, lipids, and liver enzymes) should be closely monitored in individuals with H. pylori infection, especially those with coexisting MASLD, with testing being performed every 6 months. Furthermore, early eradication therapy may improve metabolic health.

Moreover, we acknowledge several limitations in this study. First, due to the retrospective study design, the use of acid-suppressing and antibiotic medications before the 13C-urea breath test and the history of previous eradication treatments were not recorded, which may have led to an underestimation of the prevalence of H. pylori infection. Second, the target population of this retrospective study included healthy adults at the Health Examination Center of the Second Affiliated Hospital of Nanchang University, and participants who voluntarily underwent health examinations may have a higher economic status and health protection awareness than the general Chinese population, which may elicit questions concerning the representativeness of the study population. Third, due to the cross-sectional design, we were unable to establish causality between H. pylori infection and metabolic disturbances. Although we adjusted for known confounding factors, unmeasured confounders (such as genetic factors, lifestyle factors and environmental exposures) may still be present. Future research should further investigate the causal relationship between H. pylori infection and metabolic disturbances and validate its impact on metabolic parameters via interventional studies (such as by investigating H. pylori eradication therapy).

CONCLUSION

In summary, our study revealed that H. pylori infection is associated with older age and demonstrates a U-shaped BMI relationship (a higher prevalence of infection in obese and underweight individuals). Elevated glucose, diastolic blood pressure, and obesity levels are independent risk factors [odds ratio (OR) = 1.016-1.079], whereas high HDL levels confer protection (OR = 0.837). Additionally, low weight may increase susceptibility via malnutrition or gastrointestinal dysfunction. These findings highlight the dual metabolic role of H. pylori in promoting dyslipidemia, insulin resistance, and MASLD progression. Targeted screening in high-risk populations (including elderly, obese, and underweight populations) may optimize metabolic health interventions. Future longitudinal and mechanistic studies are needed to confirm causality and explore gut microbiota-inflammation pathways.

ACKNOWLEDGEMENTS

The authors express their sincere gratitude for the contributions made by the participants and recorders to this research. Their full cooperation and mutual understanding were highly important for the successful completion of the study.