Helicobacter pylori (H pylori) is a gram-negative bacterium that primarily colonizes the gastric mucosa. It is one of the most common bacterial infections, with estimates suggesting half to two-thirds of the global population is infected by H pylori. H pylori is typically transmitted via fecal-oral routes and less commonly by oral-oral, gastric-oral, or zoonotic transmission. Infected patients are usually asymptomatic but may present with abdominal pain and cramps, bloating, nausea and vomiting, or unintentional weight loss. H pylori is recognized as a major pathogen responsible for gastrointestinal disorders such as gastritis and peptic ulcer disease – accounting for 90-95% of duodenal ulcers and 70-85% of gastric ulcers. However, the most significant concern associated with infection is the increased risk of gastric cancers such as gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma.
The link between H pylori infection and gastric malignancy is well-established; epidemiological studies estimate >75% of gastric cancers are related to infection. In 1994, the World Health Organization recognized H pylori as a group 1 carcinogen, indicating a strong association with cancer development. The mechanisms by which H pylori contributes to cancer development are multifaceted. Adhesion molecules including SabA, BabA, and OipA contribute to the formation of membrane attachments that allow the bacterium to avoid immune destruction and colonize epithelium. H pylori neutralizes gastric acid through excessive urease production, promoting its survival and proliferation. The host immune response to urease incites an inflammatory reaction that stimulates release of cytokines (IL-8, IL-1, IL-6, and TNF-alpha) and perpetrates tissue injury. The chronic inflammation triggered by persistent H pylori infection may lead to progressive gastric mucosa destruction, potentially resulting in gastric atrophy and intestinal metaplasia. Additionally, specific strains, characterized by the presence of cytotoxin-associated gene A (CagA) and the vacuolating cytotoxin A (VacA), increase the risk of gastric cancer in infected patients. It remains unclear if H pylori infection is associated with other cancers; however, studies suggest infection may increase the risk of pancreatic and colorectal cancer, while decreasing the risk of esophageal adenocarcinoma.
Treatment of H pylori should be recommended to all patients positive for infection. Eradication of H pylori is shown to significantly decrease gastric cancer risk in infected individuals without precancerous lesions. One randomized clinical trial found that patients who received eradication therapy had a gastric cancer incidence of 1.6% as compared to 2.4% in the placebo group. Another long-term trial showed that eradication therapy reduced the incidence of gastric cancer by almost 50% over 22 years of follow-up. Furthermore, there is strong evidence to suggest MALT lymphoma can be completely cured by eradication of H pylori in early stages of infection. Several treatment options are available to eradicate H pylori, involving a combination of antibiotics, bismuth compounds, and proton pump inhibitors (PPIs). The addition of PPIs helps stabilize gastric pH to enhance the effectiveness of commonly used antibiotics such as clarithromycin, amoxicillin, and metronidazole. Careful selection of eradication therapy is necessary due to high rates of antibiotic resistance; guidelines recommend avoiding clarithromycin-based regimens if local resistance rates exceed 15% or the patient has past exposure to macrolide therapy. The prevalence of H pylori and escalation of antibiotic resistance support the need for further preventive measures. Research for a potential vaccine appears promising and may prove beneficial in reducing H pylori prevalence and preventing its associated complications.
Helicobacter pylori (H pylori) is a gram-negative bacterium that primarily colonizes the gastric mucosa. It is one of the most common bacterial infections, with estimates suggesting half to two-thirds of the global population is infected by H pylori. H pylori is typically transmitted via fecal-oral routes and less commonly by oral-oral, gastric-oral, or zoonotic transmission. Infected patients are usually asymptomatic but may present with abdominal pain and cramps, bloating, nausea and vomiting, or unintentional weight loss. H pylori is recognized as a major pathogen responsible for gastrointestinal disorders such as gastritis and peptic ulcer disease – accounting for 90-95% of duodenal ulcers and 70-85% of gastric ulcers. However, the most significant concern associated with infection is the increased risk of gastric cancers such as gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma.
The link between H pylori infection and gastric malignancy is well-established; epidemiological studies estimate >75% of gastric cancers are related to infection. In 1994, the World Health Organization recognized H pylori as a group 1 carcinogen, indicating a strong association with cancer development. The mechanisms by which H pylori contributes to cancer development are multifaceted. Adhesion molecules including SabA, BabA, and OipA contribute to the formation of membrane attachments that allow the bacterium to avoid immune destruction and colonize epithelium. H pylori neutralizes gastric acid through excessive urease production, promoting its survival and proliferation. The host immune response to urease incites an inflammatory reaction that stimulates release of cytokines (IL-8, IL-1, IL-6, and TNF-alpha) and perpetrates tissue injury. The chronic inflammation triggered by persistent H pylori infection may lead to progressive gastric mucosa destruction, potentially resulting in gastric atrophy and intestinal metaplasia. Additionally, specific strains, characterized by the presence of cytotoxin-associated gene A (CagA) and the vacuolating cytotoxin A (VacA), increase the risk of gastric cancer in infected patients. It remains unclear if H pylori infection is associated with other cancers; however, studies suggest infection may increase the risk of pancreatic and colorectal cancer, while decreasing the risk of esophageal adenocarcinoma.
Treatment of H pylori should be recommended to all patients positive for infection. Eradication of H pylori is shown to significantly decrease gastric cancer risk in infected individuals without precancerous lesions. One randomized clinical trial found that patients who received eradication therapy had a gastric cancer incidence of 1.6% as compared to 2.4% in the placebo group. Another long-term trial showed that eradication therapy reduced the incidence of gastric cancer by almost 50% over 22 years of follow-up. Furthermore, there is strong evidence to suggest MALT lymphoma can be completely cured by eradication of H pylori in early stages of infection. Several treatment options are available to eradicate H pylori, involving a combination of antibiotics, bismuth compounds, and proton pump inhibitors (PPIs). The addition of PPIs helps stabilize gastric pH to enhance the effectiveness of commonly used antibiotics such as clarithromycin, amoxicillin, and metronidazole. Careful selection of eradication therapy is necessary due to high rates of antibiotic resistance; guidelines recommend avoiding clarithromycin-based regimens if local resistance rates exceed 15% or the patient has past exposure to macrolide therapy. The prevalence of H pylori and escalation of antibiotic resistance support the need for further preventive measures. Research for a potential vaccine appears promising and may prove beneficial in reducing H pylori prevalence and preventing its associated complications.
References
Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39. https://journals.lww.com/ajg/fulltext/2017/02000/acg_clinical_guideline__treatment_of_helicobacter.12.aspx
Lamont JT. Bacteriology and epidemiology of Helicobacter pylori infection. Wolters Kluwer: UpToDate. 2022 Aug. https://www-uptodate-com.jerome.stjohns.edu/contents/bacteriology-and-epidemiology-of-helicobacter-pylori-infection
Polk DB, Peek RM. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010 Jun;10(6):403-14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957472/
Reyes VE. Helicobacter pylori and its role in gastric cancer. Microorganisms. 2023 May;11(5):1312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10220541/
Wroblewski LE, Peek RM, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010 Oct;23(4):713-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952980/