Back to Journals » Journal of Inflammation Research » Volume 15

Helicobacter pylori Infection as a Risk Factor for Abnormal Serum Protein Levels in General Population of China

Authors Liu H, Qin Y , Yang J, Huang G, Wei X, Wang L, Li W

Received 23 December 2021

Accepted for publication 16 March 2022

Published 26 March 2022 Volume 2022:15 Pages 2009—2017

DOI https://doi.org/10.2147/JIR.S355446

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Ning Quan



He Liu,* Yan Qin,* Jie Yang, Guoxiu Huang, Xiaoying Wei, Lulu Wang, Wei Li

Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Health Management, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wei Li; Lulu Wang, Email [email protected]; [email protected]

Background: Helicobacter pylori (HP) infection is considered as a risk factor for nutritional and metabolic abnormalities, and serum protein is an important marker of the nutritional and immune status. It is still unknown whether HP infection affects serum protein levels.
Methods: The participants who underwent health screening from July 2020 to August 2021 were included, among whom, 1485 subjects with 14C-urea breath test (14C-UBT) values ≥ 100 disintegrations per minute (dpm) were defined as HP-positive cases, and 4864 cases with 14C-UBT values < 100 dpm were defined as HP-negative cases. Anthropometric measurements were taken, and biochemical parameters of the blood were analyzed for all subjects. Categorical variables were compared using the χ 2 test and continuous variables using Student’s t test. Logistic regression analysis was used to determine the effect of HP infection on serum proteins.
Results: Age, the proportion of female, globulin levels, total cholesterol levels, and low-density lipoprotein cholesterol levels were significantly higher in the HP infected group than in the non-infected group (P < 0.05). Height, weight, body mass index, hip circumference, albumin levels, albumin to globulin ratio, triglycerides levels, and uric acid levels were significantly higher in the non-infected group than in the infected group (P < 0.05). Multifactorial analysis revealed that HP infection was significantly associated with the risk of decreased serum albumin levels (odds ratio [OR] = 0.809, P = 3.51× 10− 4); HP infection was significantly associated with the risk of increased serum globulin levels (model 1: OR = 1.257, P = 1.39× 10− 4); and HP infection was significantly associated with the risk of decreased albumin/globulin ratio (OR= 0.775, P = 2.30× 10− 5).
Conclusion: HP infection was significantly associated with lower serum albumin levels, elevated globulin levels, and lower albumin/globulin ratio. Thus, it is an important factor affecting nutritional metabolism.

Keywords: Helicobacter pylori, nutrition, serum albumin, serum globulin, albumin/globulin ratio

Background

Helicobacter pylori (HP) is a Gram-negative bacterium found in the gastric mucosa. It is prevalent worldwide and is responsible for infecting more than 50% of the world’s population encompassing up to 80% of the population in developing countries and about 40% in the developed countries. HP prevalence in Asian populations is approximately 53%. The prevalence of HP infection in the Chinese population is higher than the Asian population average at around 60%.1,2 The prevalence of HP infection has been reported to increase with age, gradually increasing from 0 to 39 years, peaking at 39 years (59.3%) and gradually decreasing after 60 years.3 HP was recognized as a group I human carcinogen by the World Health Organization’s International Agency for Research on Cancer. About 50% of gastric cancers are associated with HP. It has been reported that HP infection enhances Th1-type immune response during carcinogenesis leading to apoptosis of gastric epithelial cells, which further leads to cell proliferation to compensate for cell loss4,5. The altered gastric environment caused by damage to the structure and function of the gastric epithelium may affect the absorption of nutrients and drugs and the production of hormones closely associated with growth regulation in the stomach. Chronic HP infection leads to decreased secretion of gastric acid, which may cause an increase in the levels of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin and interleukin.6 The surge in inflammatory cytokines may lead to metabolic changes and alterations in systemic immune responses, which are responsible for the formation of malignant tumors.7,8

Figure 1 Impact of HP infection on the correlation of common clinical variables. (A) Correlation Heatmap of clinical variables in participants with HP positive. (B) Correlation Heatmap of clinical variables in participants with HP negative. Red represented positive correlation and blue represented negative correlation. Numbers represented correlation coefficients. Larger circles indicated larger correlation coefficients. A cross indicated that the correlation did not reach the level of significance.

Recent preliminary studies have shown that HP infection causes systemic metabolic and nutritional disorders. Dutta SK study has reported a higher prevalence of HP infection in obese patients.9 In contrast, other study revealed that HP eradication significantly increased the prevalence of obesity in peptic ulcer patients, which was attributed to the increase in body mass index (BMI) and/or enhanced appetite in asymptomatic patients due to elevated plasma ghrelin levels and decreased leptin levels.10,11 Franceschi et al showed that HP infection led to impaired absorption of vitamin B12, vitamin C, vitamin E, beta-carotene, folic acid, zinc, selenium, and other nutrients.12 A recent meta-analysis showed that the prevalence of HP infection was significantly higher in patients with type 2 diabetes compared to non-diabetic patients.13 To date, many epidemiological studies have reported the association among insulin resistance, metabolic syndrome, and HP infection.14

Serum proteins are important for maintaining normal physiological status. The concentration of serum proteins is approximately 60–80 mg/mL, of which approximately 50–60% is albumin and 40% is globulin (10–20% is immunoglobulin G, IgG).15 Recent data highlight the importance of measuring serum albumin levels for prognostic assessment of certain diseases. For example, the Kidney Disease Prognostic Quality Initiative guidelines suggest that monitoring of serum albumin levels is a valid and clinically useful tool for assessing protein-energy nutritional status in patients undergoing dialysis.16 However, the correlation between HP infection and serum proteins remains unclear. In a study on the relationship between HP infection and serum albumin levels in hemodialysis patients,17 HP infection was significantly and negatively associated with serum albumin levels. Another study comprising 98 hemodialysis patients revealed that HP infection was present in 39 patients, but there were no significant differences in nutritional markers between the HP-positive group and the HP-negative group17. The aforementioned study has some limitations, such as small sample size and the study mainly comprised patients with renal disease, which is recognized as an important factor affecting albumin levels. The relationship between HP infection and serum protein levels remains unclear due to the above limitations.

Therefore, the present study was designed to analyze the correlation between HP infection and serum protein levels based on clinical data from a large number of patients. Our study may lay the foundation for further studies planned to elucidate the effect of HP infection on systemic nutritional and immune profiles.

Methods

Study Design and Population

The participants aged 12–93 years who underwent annual health check-up (including 14C urea breath test [UBT]) at the People’s Hospital of Guangxi Zhuang Autonomous Region from July 2020 to August 2021 were screened. The patients with ≥ 100 disintegrations per minute of 14C-UBT were defined as positive for HP infection (case) and those with <100 disintegrations per minute were defined as negative for HP infection (control). Participants in the HP positive group were matched 1:3 to those in the HP negative group. Inclusion criterion was detection of 14C-UBT and H. pylori. Participants with hepatobiliary disease (hepatitis, jaundice, cholecystitis, gallstones), abnormal liver function (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 1.5 times the upper limit of normal), and abnormal kidney function (Cr > the upper limit of normal) were excluded. This study was approved by the Ethics Committee of Guangxi Zhuang Autonomous Region People’s Hospital & Guangxi Academy of Medical Sciences (Number KY-ZC-2020-64). All participants provided written informed consent. For participants under 18 years of age, informed consent was provided by a parent or legal guardian. The study complies with the Declaration of Helsinki.

Anthropometric and Laboratory Measurements

The anthropometric measurements of each participant were taken by professional medical staff. The details of systemic or previous diseases such as diabetes mellitus, hypertension, hepatitis, jaundice, cholecystitis, and/or biliary stones were recorded. BMI was calculated as weight in kilograms divided by the square of height in meters (kg/m2). The waist circumference (WC) was measured in centimeters at the level of the umbilicus. The hip circumference (HC) was the straight-line distance between the outermost projecting points of the left and right thigh. Blood pressure was measured three times while the subject was seated and the average of the last two measurements was calculated. Blood samples were collected after overnight fasting. The results of serum biomarkers were collected from the hospital information system. The collected biomarkers included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total serum protein, albumin (ALB), globulin, albumin to globulin ratio (AGR), blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA) and glycosylated hemoglobin (HbA1c).

Statistical Analysis

Normally distributed continuous variables are expressed as mean ± standard deviation (SD). They were compared using analysis of variance or t-test and the between-group comparisons were evaluated by chi-square test. Binary logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) Corrections were made for nine variables (age, sex, BMI, ALT, AST, TG, TC, LDL-C, and HDL-C) that were considered as potential confounders of serum proteins’ levels. All analyses were done using SPSS, version 24.0 (SPSS Inc., Chicago, IL, USA). Differences with two-sided P value < 0.05 were considered significant.

Results

Clinical Characteristics of the Study Population

In total, 6349 subjects (4864 negative and 1485 positive for HP infection) were included in this study. The baseline characteristics of the participants in both groups are presented in Table 1. We found a significant correlation between ALB levels and HP infection with significantly lower ALB levels in the HP positive group than in the HP negative group (P=3.51×10−4). Age, the proportion of female, globulin levels, TC levels, and LDL levels were significantly higher in the HP-infected group than in the non-infected group (P<0.05). In contrast, Height, Weight, HC, BMI, AGR, triglycerides levels, and uric acid levels were significantly higher in the non-infected group than in the infected group (P < 0.05). Furthermore, no correlation was found between total protein levels and HP infection (P > 0.05).

Table 1 Comparison of Clinical Characteristics of Subjects Stratified by the Presence and Absence of Helicobacter pylori Infection

Impact of HP Infection on the Correlation of Common Clinical Variables

To assess the impact of HP infection on the correlation of common clinical variables, we divided the population into two cohorts according to the presence or absence of HP infection and performed independent correlation analyses. In both cohorts, we found a significant positive correlation between TP and ALB as well as GLB and a significant negative correlation between TP and ARG (P<0.05, Figure 1A-B). ALB was significantly negatively correlated with GLB (P<0.05). Interestingly, HP infection might have an impact on the correlation between waist circumference (WC), hip circumference (HC) and BMI. In the non-HP-infected cohort, WC was significantly and strongly positively associated with HC and BMI (HC: r=0.79; BMI: r=0.86). However, in the HP infection cohort, WC was weakly positively correlated with HC (r=0.29) and moderately positively correlated with BMI (r=0.33). In the both cohort, ALB had a weak positive correlation with cholesterol. HbA1c is weakly and positively correlated with AGR.

Association Between Age and HP Infection

Stratified analysis was used to elucidate the relationship between HP infection and age (Table 2). Analysis was done after stratifying the subjects by age. Participants were divided into the following five groups: <20 years, 20–29 years, 30–39 years, 40–49 years, and ≥50 years. Stratified analysis showed significant difference in HP infection between the 30–39 years and ≥50 years’ age groups (P=0.002). The subjects aged ≥50 years had a higher incidence of HP infection than those aged 30–39 years.

Table 2 Analysis of Helicobacter pylori Infection Stratified by Age

Association Between HP Infection and Albumin Levels

Binary logistic regression was used to analyze the association between HP infection and albumin levels. As shown in Table 3, in univariate analysis, HP infection was significantly associated with the risk of decreased serum albumin levels without adjusting for confounding factors (model 1: OR = 0.809, 95% CI = 0.720–0.909, P = 3.51×10−4). The OR remained significant after adjusting for age and sex (model 2: OR = 0.852, 95% CI = 0.755–0.962, P=0.010); after adjusting for age, sex, BMI, ALT, and AST (model 3: OR = 0.857, 95% CI = 0.755–0.973, P = 0.017); and even after adjusting for age, sex, BMI, ALT, AST, TG, TC, LDL-C, and HDL-C (model 4: OR = 0.858, 95% CI = 0.755–0.976, P = 0.020).

Table 3 Helicobacter pylori Infection Poses Risk of Reduced Albumin Levels

Association Between HP Infection and Globulin Levels

Binary logistic regression was used to analyze the association between HP infection and globulin levels. As shown in Table 4, in univariate analysis, HP infection was significantly associated with a risk of increased serum globulin levels without adjusting for confounding factors (model 1: OR = 1.257, 95% CI = 1.118–1.415, P = 1.39×10−4). The OR remained significant after adjusting for age and sex (model 2: OR = 1.232, 95% CI = 1.093–1.389, P = 0.001); after adjusting for age, sex, BMI, ALT, and AST (model 3: OR = 1.223, 95% CI = 1.079–1.386, P= 0.002), and even after adjusting for age, sex, BMI, ALT, AST, TG, TC, LDL-C, and HDL-C (model 4: OR = 1.211, 95% CI = 1.068–1.373, P = 0.003).

Table 4 Helicobacter pylori Infection Poses Risk of Increased Globulin Levels

Association Between HP Infection and Total Protein Levels

Binary logistic regression was used to analyze the correlation between HP infection and total protein levels. As shown in Table 5, no significant correlation was found between HP infection and total serum protein levels in the univariate analysis and even after adjusting for confounding factors (P > 0.05 in all cases).

Table 5 The Risk of Helicobacter pylori Infection on Total Protein Levels

Association Between HP Infection and Albumin/Globulin Ratio

Binary logistic regression was used to analyze the association between HP infection and albumin/globulin ratio. As shown in Table 6, in the univariate analysis, HP infection was significantly associated with the risk of decrease in albumin/globulin ratio without adjusting for confounding factors (model 1: OR = 0.775, 95% CI = 0.689–0.872, P = 2.30×10−5). The OR remained significant after adjusting for age and sex (model 2: OR = 0.803, 95% CI = 0.710–0.908, P = 4.47×10−4); after adjusting for age, sex, BMI, ALT, and AST (model 3: OR = 0.795, 95% CI = 0.700–0.904, P = 4.51×10−4); and even after adjusting for age, sex, BMI, ALT, AST, TG, TC, LDL-C, and HDL-C (model 4: OR = 0.803, 95% CI = 0.706–0.914, P = 0.001).

Table 6 Helicobacter pylori Infection Poses Risk of Reduction in Albumin to Globulin Ratio

Discussion

HP is the dominant bacterial species of the gastric microbiota, and HP infection can lead to inhibition of gastric acid secretion, thereby causing chronic inflammation of the gastric mucosa and altering the gastric microenvironment.18 Recent research has been focused on the fact that HP infection causes changes in the gastric environment and that HP plays an important role in maintaining the nutritional balance in the gastric environment.19 The mechanisms underlying the nutritional and metabolic changes caused due to HP infection are yet unclear. To the best of our knowledge, this is the first study to investigate the effect of HP infection on the levels of metabolic and nutrition-related serum proteins in a large Chinese population.

Our findings revealed that HP infection affected the lipids’ levels, wherein TC and LDL-C levels increased significantly and TG levels decreased significantly in the HP-infected group. A Korean study that included 15,195 participants reported that HP-positive participants had significantly higher BMI, WC, TC, LDL-C, and HDL-C levels than the seronegative participants. After adjusting for the confounders, high TC, low HDL-C, and high LDL-C levels were associated with HP seropositivity.20 Another study comprising 15,679 participants from Japan, wherein lipid profiles and HP infection status in generally healthy individuals were assessed, revealed that HP infection had a significant positive effect on LDL-C and TC levels, and a negative effect on HDL-C and TG levels.21 HP infection was also found to be positively associated with low HDL-C levels in the study by Zhao et al. The findings of our study are consistent with those of the aforementioned studies. Notably, our results further suggest that HP infection may cause metabolic abnormalities as indicated by both high levels of serum LDL-C and low levels of serum HDL-C, which are the risk factors for atherosclerosis and coronary artery disease. Thus, the results of this study suggest that HP infection can affect the lipid profile and may indirectly lead to various diseases caused due to abnormal lipid metabolism.

In our study, serum albumin levels and AGR were significantly lower in HP-positive participants than in HP-negative participants, and low levels of serum albumin and low AGR were associated with HP positivity after adjusting for confounding factors, including age, sex, BMI, ALT, AST, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Therefore, HP infection may be a risk factor for low serum albumin levels. In a study by Furuta et al, levels of serum total protein, albumin, and total cholesterol were significantly higher in subjects with HP eradication.22 In another study, the incidence of hypoproteinemia was significantly higher in HP-positive patients than in HP-negative patients and it decreased significantly after HP eradication, thus suggesting that HP eradication restores gastrointestinal digestion and absorption, which may be instrumental in improving nutritional parameters.23 The authors hypothesized that HP infection may lead to impaired gastric acid secretion because the median gastric pH of patients with hypoproteinemia was much higher than the patients with normal protein levels. Thus, HP infection may reduce albumin levels by increasing gastric pH and thereby affecting gastric digestion and absorption. In addition, damage to the gastric mucosa caused by HP infection weakens the digestive and absorptive functions of the stomach, resulting in a decrease in serum albumin.24 When HP contacts the gastric mucosal epithelium, the epithelium undergoes cytoskeletal reorganization and tyrosine phosphorylation, which in turn activates nuclear factor-κB (NF-κB) and leads to the secretion of chemokines such as IL-8 by epithelial cells, thereby chemotactic and activating inflammatory cells, causing them to migrate from the blood vessels to the gastric epithelium. Neutrophils and macrophages release a variety of inflammatory mediators and cytokines, including prostaglandins, leukotrienes, blood alkane boluses, TNF-α and various ILs, which have direct cytotoxic effects on gastric epithelial cells.25 Finally, HP infection can promote the formation of microproteinuria leading to a decrease in serum albumin levels. Balat et al reported that a significant higher proteinuria in HP infected patients compared to non-infected individuals.26 Potential mechanisms may be indirect damage to the urinary system due to systemic inflammatory immune response induced by HP infection and direct damage to the urinary system by virulence factors released by HP.27

We found that HP infection was positively correlated with serum globulin. We speculated that the underlying mechanism was that when a foreign microbe like HP is present in the body, the immune organs of the body activate the immune mechanism to increase globulins in order to destroy the invaders.28 AGR is often used as a prognostic marker and reduced AGR is associated with poor prognosis of the disease. Interestingly, in the present study, AGR was significantly lower when albumin levels were reduced and globulin levels were increased, thus, indicating the poor prognosis of the patients. In contrast, the total protein levels in the HP positive group were lower than those in the HP negative group, but the difference was not statistically significant. By analyzing TP, ALB, globulin, and AGR simultaneously in the HP infected group, we were able to reflect the nutritional status and inflammatory response of the patients more accurately and comprehensively.

This study has some limitations. First, many variables that may be related to or affect serum proteins had not been evaluated, including skin fold thickness, lean body mass, eating habits, smoking, etc. Second, globulin electrophoresis was not performed, so we could not identify the components of the globulin that had changed. Third, the clinical significance of serum protein abnormalities due to HP infection needs to be further explored. In the next study, we will carry out this in patients undergoing surgery to investigate the rate of postoperative complications and wound healing in people with HP infection.

Conclusion

Our analysis of a large cohort based on the general Chinese population showed that HP infection was an independent risk factor for reduced serum albumin levels, increased serum globulin levels and reduced AGR. The results of this study have important implications for the elucidation of the effects of HP infection on systemic nutrition-immunity and provide a basis for exploring the impact of HP infection on surgical complications and the recovery process in the disease state.

Data Sharing Statement

The dataset supporting the conclusions of this article is included within the article.

Ethics Approval and Consent to Participate

This study was approved by the Ethics and Human Subject Committee of Guangxi Zhuang Autonomous Region People’s Hospital & Guangxi Academy of Medical Sciences (Number KY-ZC-2020-64). All participants provided written informed consent.

Funding

This work was supported by the Scientific research project funded by Guangxi Zhuang Autonomous Region Health and Health Commission Self-Financed Research Projects (NO. Z20201318).

Disclosure

The authors report no conflicts of interest in this work.

References

1. Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420–429. doi:10.1053/j.gastro.2017.04.022

2. Subsomwong P, Miftahussurur M, Uchida T, et al. Prevalence, risk factors, and virulence genes of Helicobacter pylori among dyspeptic patients in two different gastric cancer risk regions of Thailand. PLoS One. 2017;12(10):e0187113. doi:10.1371/journal.pone.0187113

3. Wang X, Shu X, Li Q, et al. Prevalence and risk factors of Helicobacter pylori infection in Wuwei, a high-risk area for gastric cancer in northwest China: an all-ages population-based cross-sectional study. Helicobacter. 2021;26(4):e12810. doi:10.1111/hel.12810

4. Moss S, Calam J, Agarwal B, Wang S, Holt P. Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut. 1996;38(4):498–501. doi:10.1136/gut.38.4.498

5. Cahill RJ, Sant S, Beattie S, Hamilton H, O’Morain C. Helicobacter pylori and increased epithelial cell proliferation: a risk factor for cancer. Eur J Gastroenterol Hepatol. 1994;6(12):1123–1128. doi:10.1097/00042737-199412000-00010

6. Sugimoto M, Furuta T, Yamaoka Y. Influence of inflammatory cytokine polymorphisms on eradication rates of Helicobacter pylori. J Gastroenterol Hepatol. 2009;24(11):1725–1732. doi:10.1111/j.1440-1746.2009.06047.x

7. Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, et al. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut. 2018;67(2):226–236. doi:10.1136/gutjnl-2017-314205

8. Kim TJ, Sinn DH, Min YW, et al. A cohort study on Helicobacter pylori infection associated with nonalcoholic fatty liver disease. J Gastroenterol. 2017;52(11):1201–1210. doi:10.1007/s00535-017-1337-y

9. Dutta SK, Arora M, Kireet A, Bashandy H, Gandsas A. Upper gastrointestinal symptoms and associated disorders in morbidly obese patients: a prospective study. Dig Dis Sci. 2009;54(6):1243–1246. doi:10.1007/s10620-008-0485-6

10. Dhurandhar N, Bailey D, Thomas D. Interaction of obesity and infections. Obes Rev. 2015;16(12):1017–1029. doi:10.1111/obr.12320

11. Jeffery PL, McGuckin MA, Linden SK. Endocrine impact of Helicobacter pylori: focus on ghrelin and ghrelin o-acyltransferase. World J Gastroenterol. 2011;17(10):1249–1260. doi:10.3748/wjg.v17.i10.1249

12. Franceschi F, Annalisa T Di Rienzo Teresa D, et al. Role of Helicobacter pylori infection on nutrition and metabolism. World J Gastroenterol. 2014;20(36):12809. doi:10.3748/wjg.v20.i36.12809

13. Li J-Z, Li J-Y, Wu T-F, et al. Helicobacter pylori infection is associated with type 2 diabetes, not type 1 diabetes: an updated meta-analysis. Gastroenterol Res Pract. 2017;2017:1–15. doi:10.1155/2017/5715403

14. Marietti M, Gasbarrini A, Saracco G, Pellicano R. Helicobacter pylori infection and diabetes mellitus: the 2013 state of art. Panminerva Med. 2013;55(3):277–281.

15. Greenough C, Jenkins RE, Kitteringham NR, Pirmohamed M, Park BK, Pennington SRJP. A method for the rapid depletion of albumin and immunoglobulin from human plasma. Proteomics. 2004;4(10):3107-3111.

16. Levey AS, Coresh J, Bolton K, et al. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl. 1):i–ii+ S1–S266.

17. Jalalzadeh M, Saber HR, Vafaeimanesh J, Mirza MF, Falaknazi K. Association of Helicobacter Pylori Infection and Serum Albumin in Patients on Hemodialysis. Iran J Kidney Dis. 2010;4:312–316.

18. Noto JM, Peek RM, Leong JM. The gastric microbiome, its interaction with Helicobacter pylori, and its potential role in the progression to stomach cancer. PLoS Pathog. 2017;13(10):e1006573. doi:10.1371/journal.ppat.1006573

19. Yu Y, Cai J, Song Z, Wang J, Wu L. Association of Helicobacter pylori infection with metabolic syndrome in aged Chinese females. Exp Ther Med. 2019;17(6):4403–4408. doi:10.3892/etm.2019.7509

20. Lim SH, Kim N, Kwon JW, et al. Positive association between Helicobacter pylori infection and metabolic syndrome in a Korean population: a multicenter nationwide study. Dig Dis Sci. 2019;64(8):2219–2230. doi:10.1007/s10620-019-05544-3

21. Shimamoto T, Yamamichi N, Gondo K, et al. The association of Helicobacter pylori infection with serum lipid profiles: an evaluation based on a combination of meta-analysis and a propensity score-based observational approach. PLoS One. 2020;15(6):e0234433. doi:10.1371/journal.pone.0234433

22. O’Connor A, Furuta T, Gisbert JP, O’Morain C. Review–treatment of Helicobacter pylori infection 2020. Helicobacter. 2020;25:e12743. doi:10.1111/hel.12743

23. Furuta T, Shirai N, Xiao F, Takashima M, Hanai H. Effect of Helicobacter pylori infection and its eradication on nutrition. Aliment Pharmacol Ther. 2002;16(4):799–806. doi:10.1046/j.1365-2036.2002.01222.x

24. Gyulai Z, Klausz G, Tiszai A, et al. Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer. Eur Cytokine Netw. 2004;15(4):353–358.

25. Hofman V, Lassalle S, Selva E, et al. Involvement of mast cells in gastritis caused by Helicobacter pylori: a potential role in epithelial cell apoptosis. J Clin Pathol. 2007;60(6):600–607. doi:10.1136/jcp.2006.040741

26. Balat MN, Fahmy Zanaty MA, EL-Antouny NG, Ahmed HK. Association between proteinuria and active Helicobacter pylori infection in non-diabetic patients. Zagazig Univ Med J. 2019;25(1):79–84. doi:10.21608/zumj.2019.23702

27. Bagirova M, Allahverdiyev AM, Abamor ES, Aliyeva H, Unal G, Tanalp TD. An overview of challenges to eradication of Helicobacter pylori infection and future prospects. Eur Rev Med Pharmacol Sci. 2017;21(9):2199–2219.

28. Moyat M, Velin D. Immune responses to Helicobacter pylori infection. World J Gastroenterol. 2014;20(19):5583–5593. doi:10.3748/wjg.v20.i19.5583

Creative Commons License © 2022 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.