Influence of Helicobacter pylori Infection and Eradication Therapy on Nutrition and Metabolic Parameters

The prevalence of Helicobacter pylori is not only reducing in Western countries, such as the United States and Europe. In East Asian countries, such as Korea and Japan, H. pylori has been significantly and dramatically decreasing to around 10% to 30%, due to improved socioeconomic conditions and educational environment, and an increase in patients receiving eradication therapy for H. pylori infection.¹ International clinical guidelines for H. pylori infection strongly recommend eradication as the first-line treatment to prevent H. pylori-associated diseases for all infected patients.² The major impact of eradication therapy in clinical practice is its preventive effect on gastric cancer development. Patients who undergo eradication therapy have a significantly reduced risk of gastric cancer (a relative risk of approximately half).³ Recently, diet-related gastrointestinal changes and H. pylori infection have received substantial attention. Chronic H. pylori infection and the eradication treatment can both affect nutritional status and change the environment of the gastrointestinal tract.

Various changes occur in the body after H. pylori eradication. Eradication treatment markedly reduces the infiltration of inflammatory cells in the gastric mucosa, decreases gastric and serum pro-inflammatory cytokine levels, and simultaneously recovers the ability to secrete gastric acids at the same time. Endocrinologically, ghrelin, an orexigenic peptide that is released primarily from gastric endocrine cells, is important in the pathogenesis of protein energy wasting and sarcopenia in the elderly. Low serum ghrelin levels increase the risk of cardiovascular mortality and morbidity.⁴ Importantly, gastric and serum ghrelin levels significantly differ depending on H. pylori infection status. Serum and gastric ghrelin levels are generally lower in patients who are H. pylori-positive, especially in those with severe atrophy, than H. pylori-negative and post-eradication patients.⁵ Clinically, hyperlipidemia, hyperproteinemia, an increased body weight, and a higher body mass index are often observed in patients post-eradication.⁶ This may be attributed to an increase in ghrelin levels after eradication, followed by an increased appetite and greater food intake.⁵ Nutritional status after eradication may depend on increased serum and gastric ghrelin levels and other biological conditions, such as an improvement in gastrointestinal motility, a change in the gastric and gut microbiome profile, and enhanced absorption ability.^7,8

Recently, an increasing number of studies have focused on the gastric and gut microbiota. The composition of the microbiota is related to nutritional status and gastrointestinal changes following eradication. Successful eradication effectively improves gastric and gut microbiota dysbiosis. In a meta-analysis, Actinobacteria decreased 1 to 3 months after H. pylori eradication but no changes were observed in the level of Bacteroidetes, Proteobacteria, or Firmicutes before versus after eradication.⁹ In contrast, after 6 months, Actinobacteria and Bacteroidetes decreased, and Firmicutes increased.⁹ Additionally, patients with diabetes and hyperlipidemia show a different gut microbiota profile to that of healthy individuals. Moreover, there is a possibility that the gut microbiota profile will change following eradication therapy to become closer to that found in patients with metabolic abnormalities. This aspect warrants further research.

As mentioned above, prolonged H. pylori infection and its eradication can affect nutritional status by changing the gastrointestinal tract environment, which can significantly impact an individual's life expectancy. Numerous trials have investigated the effects of H. pylori eradication on body weight, body mass index, blood pressure, nutritional status, lipid markers (e.g., total cholesterol, low density lipoprotein [LDL], high density lipoprotein, and triglyceride), and serological nutritional markers (e.g., albumin, transthyretin, retinol-binding protein, transferrin, apolipoprotein [ApoC-II and ApoC-III]) and the results have been conflicting. To date, no definite conclusions regarding nutritional changes after eradication have been reached. The quality of the evidence has been limited by the small sample sizes, the varied and limited nutritional parameters examined, and the different follow-up among previous trials. In this issue of Gut and Liver, a retrospective study by Bae et al.¹⁰ reported that in 823 asymptomatic patients who underwent health screening before and after H. pylori eradication between 2005 and 2021, metabolic parameters including blood pressure, hemoglobin A1c, and LDL, as well as inflammatory markers including erythrocyte sedimentation rate and C-reactive protein, were significantly improved compared to those in the non-eradicated group. In contrast, compared to pre-treatment, eradication significantly increased body weight and body fat mass, irrespective of the severity of gastric atrophy, approximately 1.3 years after H. pylori eradication. The strength of this study is that it included a large number of patients. Despite showing an increasing trend in body weight and abdominal circumference, this trial showed significant improvements in blood pressure and hemoglobin A1c and LDL levels. However, this discrepancy is difficult to explain.

In general, because the rate of H. pylori re-infection after eradication in developed countries is low (less than 1% to 2%) and changes in the gastric environment in terms of gut microbiota, ghrelin, and acid inhibition ability after eradication tend to continue over time, longitudinal studies are needed to evaluate the effects of eradication on the nutritional status. However, in this study, the mean follow-up period after eradication was only 488.63 days; therefore, evaluating the true effects may be challenging. To further investigate the effects of eradication treatment on nutritional status in the future, long-term follow-up observations in a prospective study with a large number of enrolled patients are necessary.