Helicobacter pylori (HP) infection is a major cause of chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer, as well as being closely associated with a variety of extra gastrointestinal diseases [1][2]. It has been reported that approximately half of the global population is infected with HP [3]. Although the HP infection rate in China has continued to decline over the past decades (overall infection rate of 58.3% during 1983-1994 and 40.0% during 2015-2019) [4][5], the disease burden associated with HP is still significant due to the large population base. Therefore, the investigation and prevention of HP infection has become a public health issue of particular concern to the medical field in China.

HP infection has a global distribution, and the prevalence of HP infection in different populations varies greatly depending on age, family history of gastric cancer, geographic location, regional economic development, and sanitary conditions [3][6]. An epidemiologic survey in 2021 that included a total of 10,735 households (31,098 individuals) in 29 provinces in mainland China, excluding Guangxi and Xizang, showed that the prevalence of individual HP infection in the 29 provinces ranged from 25.33% to 59.61% [7]. A recent meta-analysis of the temporal and spatial distribution of HP infections in mainland China also showed that the plateau is a high-prevalence area for HP infections [8]. Eradication of HP can effectively control the disease progression associated with HP infection and is the most controllable measure to reduce the risk of gastric cancer [9]. There have been some investigations and analyses focusing on the current status of HP infection in different regions of China, but there is a lack of comparative studies on the current status and differences between HP infection in highland areas and plains. In this study, we used a multicenter cross-sectional study to explore and compare the current status and differences of HP infection in the highland and plains areas, to provide data for the prevention and control of HP infection in the highland and plains areas, and guide how to formulate public health policies and preventive and control strategies targeting. HP infection by local conditions, to prevent HP infection-related diseases and to improve the level of health.

The global prevalence of HP in adults between 2011 and 2022 is 43.1%, with similar rates for men and women. However, there is regional variability in the infection rate, with the Middle East having the highest rate of 56.1%, followed by Asia with 53.3%. The overall HP infection rate in our population is higher than the global rate, 46.7%, and is higher in rural than in urban areas, with the highest rate (>50%) in people aged 30 - 60 years. The results of the urea breath test showed that the prevalence of HP infection in the medical checkup population in different regions ranged from 25.8% to 38.82%, indicating that it is necessary to actively carry out HP screening in the medical checkup population and strengthen the post-test intervention and management, which can help to reduce the risk of gastric cancer in this opportunistic population, and it is one of the most important strategies for gastric cancer prevention and control.

This study is the first to compare the current status and differential characteristics of HP infection in a healthy physical examination population in highland and plains areas. The survey included 260 cases of health checkups in the highlands and 10,972 cases in the plains, and the results showed that the prevalence of HP infection was significantly higher in the highlands than in the plains. HP infection is influenced by many factors such as environment, cultural level, and living habits. People who live at high altitudes, have low levels of education, and eat out more frequently are usually more susceptible to HP infection than the rest of the population [7][12]. The results of this study showed that the HP infection rate in the health checkup population in the plateau region was 55.4%, which was lower than the national average infection level, which may be related to the improved hygiene and health awareness of the local population as well as the small sample size of this survey in the plateau region. Cui Ying et al. [13] showed that the HP prevalence rate in the health checkup population in the plateau region was 62.47%, which was slightly higher than the average of this study and China, which may be related to the higher proportion of patients included in the study who frequently used pickled or barbecued foods and had a history of chronic gastric disease.

In addition, some researchers have pointed out that the high rates of HP infection and gastric cancer among plateau residents are not only due to the backwardness of health and economy, but may also be related to the environmental characteristics of the plateau [14]. Plateau populations living in alpine and hypoxic environments may undergo a series of adaptive changes in their respiratory system, cardiovascular system, and metabolic characteristics [15]. A survey comparing the prevalence of HP infection among residents at different altitudes showed that the prevalence of HP infection among residents living at high altitudes was 68.67%, which was significantly higher than that of 57.33% among residents who moved to low altitudes [16]. This is consistent with the results of this study. A study investigating patients with digestive symptoms in high-altitude regions of India found a higher prevalence of HP infection through histopathology and endoscopy [17]. In addition, a recent study indicated that high-altitude hypoxia exacerbates gastric mucosal inflammation and injury by enhancing oxidative stress and inflammatory response induced by HP infection [18]. However, a previous study showed that high altitude and the colder climate do not influence on the prevalence of HP in Saudi nationals sharing similar genetic and cultural habits, which is possibly related to sample size, and differences between study areas [19]. The causal relationship between altitude and HP infection needs to be further investigated.

In the HP-infected population, the percentage of overweight or obese group was higher in the plateau region than in the plains, which may be related to the dietary habits and lifestyle in the plateau region. It is also associated with the role of the intestinal immune system in prompting the body to secrete inflammatory factors and increase insulin resistance after HP infection. The recent meta-analysis results showed that there was a positive correlation between the risk of HP infection and the prevalence of obesity development [20]. HPinfection triggers the release of the orexigenic hormone, ghrelin, which regulates the appetite [21]. Obese/overweight individuals have been shown to exhibit reduced circulating levels of ghrelin, indicating a potential association between ghrelin and obesity [22]. In addition, HP-positive individuals have been shown to exhibit reduced serum levels of leptin [23][24]. Reduced leptin levels induce appetite, which leads to overfeeding, resulting in overweight and obesity [25]. However, in a meta-analysis, previous studies were found to be geographically diverse, with more retrospective studies and fewer observational studies, and many uncontrollable confounding factors may be involved in the process of obesity development and HP infection [26], and there is still a need for large cohort studies and large-sample randomized controlled trials to study the relationship between obesity and HP.

Results are inconsistent between studies regarding the possible relationship between HP infection and smoking. No relationship between HP infection and smoking was found in the majority of cases. In this study, the smoking rate of HP-infected patients was higher in the plateau than in the plains, which was consistent with previous studies [27]. Features of high-altitude environments allow hypoxia, energy depletion, and tissue acidosis in localized tissues, which may damage intestinal epithelial cells and disrupt tight junction protein complexes, leading to intestinal barrier dysfunction [28]. In this environment accompanied by tobacco and alcohol addiction, gastric acid, and duodenal bicarbonate secretion increased, damage to the gastric mucosal barrier. Furthermore, Nicotine appears to enhance gastric invasive factors (e.g., gastric acid and pepsin secretion, duodenal gastric reflux, and free radical production) and weaken mucosal defenses (e.g., prosta-glandin synthesis, mucus production, and epidermal growth factor secretion), which may enhance colonization following H. pylori exposure [29]. Although the available data were insufficient to examine the causal relationships between smoking and the risk of HP infection, smoking cessation should be advocated to reduce HP infection; in the meantime, it is necessary to make individualized health management and intervention programs for people who smoke and are infected with HP to reduce the infection and prevalence, which in turn effectively reduces the incidence of secondary diseases, such as gastric ulcers, and gastric cancer.

In this study, it has been shown [30] that alcohol consumption destroys the barrier effect of gastric mucosa and triggers gastrointestinal diseases, and that HP infection and long-term alcohol consumption lead to the inhibition of IL10-induced CD8+ cell dysfunction and the inhibition of NKX6.3 expression-induced gastric carcinogenesis. However, the study did not find any difference between HP infection individuals from the plateau and the plains, which may be related to the small number of alcohol drinkers included in the study.

This study showed that the serum total bilirubin was significantly higher in the plateau than in the plains, but direct bilirubin lower than in the plains, and this study is similar to the findings of Zeng et al. [31], which showed that the percentage of total bilirubin abnormalities in plateau officers and soldiers at altitudes >3000 m was higher than that in the population at altitudes <1000 m. The increase of bilirubin is mainly due to the hypoxia-induced increase in secretion of erythropoietin after the organism enters the plateau, driving the compensatory mass production of red blood cells and hemoglobin, and the corresponding increase in senescence and destruction of red blood cells, and a large amount of hemoglobin is converted into indirect bilirubin, which is more than the processing capacity of the liver, and it can’t be completely converted into direct bilirubin, so the level of serum total bilirubin is elevated [32]. In addition, TBIL and DBIL in the Han population were significantly higher than those in the Xizang’s population for 3 consecutive years. Even the average level of TBIL in the Han nationality has exceeded the upper limit of the normal reference value for three consecutive years, which shows that the metabolic burden of the liver is heavier in the Han population at extremely high altitudes [33]. Studies have shown that HP infection may be associated with decreased bilirubin concentrations within the reference range [34]. The possible mechanism is that HP itself acts as an immunogen, and its virulence factor induces the recruitment of immune cells, releasing a large number of cytokines that can function far from the gastric mucosa, such as IL-6, IL-8, and tumor necrosis factor-alpha, which inhibit the activity of heme hydroxylase and reduce bilirubin production [35]. Furthermore, HP infection has been shown to result in chronic inflammation and influence bile reflux [36], which may at least in part explain the bilirubin changes, but further research relating to possible mechanisms is required.

In this study, the two groups of HP-infected patients also differed in TC, TG, LDL-C, ALT, and AST, which is related to the fact that chronic HP infection may affect lipid metabolism, stimulate the body to initiate systemic immune responses and inflammatory reactions and promote atherosclerosis [37][38]. The results of several studies at home and abroad have shown that TC, TG, and LDL-C levels are elevated in HP-infected patients, which is consistent with the results of this study [39]-[41].

This study is the first to compare and analyze the HP infection status of health check-up populations in the plateau and plains based on multicenter real-world big data, providing strong data on ethnic and regional differences in HP infection in the plateau region. The shortcomings of the study are mainly in the following three areas. First, the sample size of the highland areas included in the survey was small and from a concentrated source, and a large-scale, multiregional sampling survey has yet to be organized to provide more convincing evidence. Second, the study population did not undergo gastroscopy, so it was not possible to assess the differences in the pathologic changes in the gastric mucosa of the HP infection population in the highlands and plains. Future studies could incorporate gastroscopy and histological examination to confirm HP infection and assess the severity of gastritis and other gastric lesions to provide a more complete picture of the disease burden. Thirdly, the populations sampled (health check-up attendees) might not accurately represent wider community HP infection rates. Therefore, large-scale, multiregional sampling surveys need to be organized to better explore the current status of HP infection. In summary, the rate of HP infection is higher in the population of health checkups in the plateau region, and the population in the plateau region mostly has lifestyle-related factors such as low educational level, high percentage of smoking, a large percentage of overweight or obesity, and high percentage of eating out. The prevention and control of HP-related infection factors should be strengthened in highland areas.