Helicobacter pylori infection is a common bacterial condition that affects the lining of the stomach. It is strongly linked to long-term inflammation of the stomach (chronic gastritis), peptic ulcers, and a higher risk of stomach cancers, including gastric adenocarcinoma and a rare type of lymphoma known as MALT lymphoma. The infection is caused by Helicobacter pylori, a spiral-shaped bacterium that uses tiny tail-like structures (flagella) to move and produces an enzyme called urease. This enzyme helps the bacterium survive stomach acid by creating a more neutral environment, allowing it to damage the stomach’s protective lining and cause inflammation.
Worldwide, H. pylori is one of the most widespread bacterial infections, affecting over half of the global population. Rates are higher in developing countries, where access to clean water and proper sanitation is limited. The infection is usually acquired in childhood and spreads through person-to-person contact, often by the fecal–oral (contaminated hands, food, or water) or oral–oral (saliva) routes. Many people never develop symptoms, but when they do, these can include stomach pain, bloating, nausea, frequent burping, loss of appetite, indigestion, or unexplained weight loss.
Prevention mainly relies on good hygiene and safe food and water practices, such as washing hands before eating and after using the toilet, drinking clean water, and eating thoroughly cooked food.
Treatment usually requires medication, as the infection rarely clears on its own. The standard approach is a 10–14 day course of “triple therapy,” which combines two antibiotics (such as clarithromycin, amoxicillin, or metronidazole) with a proton pump inhibitor (PPI) to reduce stomach acid. If this fails due to antibiotic resistance, a stronger “quadruple therapy” may be used, which can include bismuth compounds or additional antibiotics. Successful treatment lowers the risk of ulcers returning and reduces the long-term chance of developing stomach cancer.
Classification
Helicobacter pylori is a spiral-shaped, Gram-negative bacterium that lives in the human stomach. It belongs to the genus Helicobacter within the family Helicobacteraceae. This genus contains several species that can infect humans and animals, but H. pylori is the best known because of its strong link to gastritis, peptic ulcers, and stomach cancer.
The species was first described in 1982 by Barry Marshall and Robin Warren, who initially named it Campylobacter pyloridis because of its resemblance to Campylobacter species. Further genetic and biochemical studies showed significant differences, leading to the creation of the genus Helicobacter in 1989, with H. pylori as its type species.
The bacterium is microaerophilic, meaning it grows best in environments with low levels of oxygen. Its spiral shape and tail-like structures, called flagella, allow it to move through the protective mucus lining of the stomach. Another important feature is its production of the enzyme urease, which helps neutralize stomach acid so it can survive in the harsh gastric environment.
H. pylori infection usually causes chronic inflammation of the stomach lining. While many people remain without symptoms, the infection can sometimes progress to more serious digestive diseases. Its presence is confirmed by breath tests, stool antigen tests, biopsies, or serology.
Epidemiology and Prevalence
Helicobacter pylori is one of the most widespread human pathogens, infecting an estimated 50% of the global population. The prevalence varies substantially across regions, largely reflecting differences in socioeconomic status, sanitation, and public health infrastructure. In high-income countries, prevalence rates typically range from 20% to 40%, whereas in low- and middle-income regions of Asia, Africa, and Latin America, rates may exceed 70% to 80%. This striking geographic disparity underscores the importance of living conditions in transmission and persistence of the infection.
Infection often starts during childhood. Once established, colonization tends to remain chronic unless specifically targeted with eradication therapy, since the bacterium has evolved mechanisms to evade host immune clearance.
Over recent decades, the prevalence of H. pylori has declined in many industrialized nations, primarily due to improvements in sanitation, widespread access to clean water, smaller household sizes, and more frequent use of antibiotics, but it remains a major public health issue in Asia, Africa, and Latin America.
Key Risk Factors
Risk factors for H. pylori infection include poor sanitation, crowded living conditions, and limited access to clean water. These conditions facilitate oral-oral or fecal-oral transmission. Crowded living conditions, such as those found in large households or shared housing environments, further increase exposure risk, especially during early childhood when initial infection most commonly occurs.
Age plays a role, with most infections acquired in childhood and prevalence generally increases with age in populations where infection is common. Lower socioeconomic status consistently correlates with higher infection rates.
Smoking and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) can exacerbate mucosal damage in individuals already infected with H. pylori, thereby increasing the likelihood of peptic ulcer disease. A family history of gastric disorders, including ulcers and cancer, may also indicate increased vulnerability, partly due to shared environmental exposure and genetic predisposition. Immunocompromised individuals represent another high-risk group, as impaired immune responses may facilitate bacterial persistence and complicate treatment outcomes.
Transmission and Pathogenesis
Helicobacter pylori spreads primarily through direct contact and uses specific bacterial factors to establish infection. The bacterium triggers a host immune response that contributes to inflammation and tissue damage in the stomach lining.
Routes of Transmission
The primary modes of H. pylori transmission are oral–oral and fecal–oral. Close person-to-person contact plays a central role, with spread often occurring within families, especially between parents and children. Saliva and gastric refluxate can harbor the bacterium, making kissing, sharing utensils, or consuming food handled by infected individuals important risk factors.
Contaminated water and food also serve as reservoirs, particularly in regions with poor sanitation and limited access to clean drinking water. In such environments, fecal contamination contributes significantly to transmission. The bacterium’s capacity to survive briefly outside the stomach allows it to persist in untreated water sources and inadequately prepared foods.
Transmission risk increases with overcrowding, poor hygiene, and low socioeconomic status. These factors explain higher infection rates in developing countries compared to developed ones.
Bacterial Mechanisms of Infection
Once introduced into the stomach, H. pylori employs several specialized mechanisms to survive, colonize, and damage the gastric mucosa. A key adaptation is its production of urease, an enzyme that hydrolyzes urea into ammonia and carbon dioxide. This reaction neutralizes gastric acid in the immediate vicinity of the bacterium, creating a localized alkaline environment that facilitates survival.
Motility is another crucial factor. The bacterium’s flagella enable it to penetrate the viscous gastric mucus layer, allowing access to epithelial cells and niches where the pH is less hostile. Adhesion proteins on the bacterial surface, such as BabA and SabA, mediate firm attachment to gastric epithelial cells, preventing clearance by peristalsis or mucus turnover.
Virulence factors injected into host cells further contribute to pathogenesis. The cytotoxin-associated gene A (CagA) protein, delivered via a type IV secretion system, disrupts host cell signaling pathways, leading to cytoskeletal changes, increased inflammation, and potentially precancerous alterations. Another factor, the vacuolating cytotoxin A (VacA), induces host cell vacuolation, apoptosis, and immune evasion. Together, these proteins play a pivotal role in tissue injury and disease progression.
Host Response
The host immune system recognizes H. pylori through pattern recognition receptors such as Toll-like receptors, which detect bacterial components and activate inflammatory signaling pathways. This results in the release of pro-inflammatory cytokines, including interleukin-8, which recruits neutrophils and other immune cells to the site of infection.
Despite vigorous immune activation, H. pylori persists by evading clearance through multiple mechanisms. The bacterium modifies its surface antigens to avoid immune detection, manipulates host immune responses, and creates localized immunosuppressive environments within the gastric mucosa. As a consequence, the infection typically becomes chronic, lasting for decades if untreated.
The chronic inflammation driven by persistent immune activation contributes directly to gastric pathology. Neutrophil and lymphocyte infiltration, coupled with oxidative stress, damages epithelial cells and disrupts mucosal integrity. Over time, these processes may lead to the formation of peptic ulcers, atrophic gastritis, and, in some individuals, progression to gastric adenocarcinoma or mucosa-associated lymphoid tissue (MALT) lymphoma.
Clinical Manifestations
Helicobacter pylori infection presents with various clinical features that range from mild discomfort to severe gastrointestinal issues. These manifestations depend on factors such as bacterial strain, host immune response, and the presence of underlying conditions.
Common Symptoms
Most individuals with H. pylori infection experience chronic gastritis, which leads to symptoms like epigastric pain, bloating, and nausea. The pain often worsens when the stomach is empty and may improve after eating.
Other frequent symptoms include belching, loss of appetite, and intermittent vomiting. Dyspepsia linked to this infection is usually persistent but varies in intensity. In some cases, symptoms resemble peptic ulcer disease.
Complications
Helicobacter pylori (H. pylori) infection is associated with a wide spectrum of gastrointestinal complications, ranging from mild gastritis to life-threatening conditions such as peptic ulcer disease and gastric cancer. The pathogenic effects of the bacterium result from its ability to colonize the gastric mucosa, produce cytotoxins, and induce chronic inflammation.
Peptic Ulcer Disease
One of the most common complications of H. pylori infection is peptic ulcer disease, which involves the formation of ulcers in the stomach (gastric ulcers) or the first part of the small intestine (duodenal ulcers). The bacterium disrupts mucosal defenses by altering gastric acid secretion and damaging the protective mucous layer, thereby exposing the epithelium to acid and pepsin. Ulceration can cause persistent epigastric pain, nausea, bloating, and, in severe cases, gastrointestinal bleeding. Hemorrhage may present as hematemesis (vomiting blood) or melena (black, tarry stools). Rarely, ulcers may progress to perforation, resulting in acute peritonitis, which requires immediate surgical intervention.
Gastric Cancer
Chronic H. pylori infection is a well-established risk factor for gastric adenocarcinoma, one of the most common forms of stomach cancer worldwide. The mechanism involves prolonged inflammation leading to a cascade of mucosal changes, including chronic gastritis, atrophy of the gastric glands, intestinal metaplasia, dysplasia, and eventually carcinoma. The risk is influenced by bacterial virulence factors, host genetic susceptibility, and environmental cofactors such as diet and smoking. H. pylori has been classified as a Group I carcinogen by the International Agency for Research on Cancer (IARC), underscoring its role in gastric carcinogenesis.
Gastric Lymphoma
In addition to adenocarcinoma, H. pylori infection is linked to mucosa-associated lymphoid tissue (MALT) lymphoma, a type of non-Hodgkin lymphoma that arises from chronic immune stimulation in the gastric mucosa. In early stages, eradication of H. pylori with antibiotic therapy can lead to regression of the lymphoma, highlighting the bacterium’s direct role in lymphomagenesis. Advanced cases may require chemotherapy, radiation, or surgical treatment.
Chronic Gastritis and Atrophy
Persistent infection frequently results in chronic gastritis, characterized by infiltration of the gastric mucosa with inflammatory cells. Over time, this process may lead to atrophic gastritis, in which gastric glands are progressively lost and replaced by fibrous or intestinal-type tissue. Atrophic gastritis reduces acid and intrinsic factor secretion, impairing digestion and vitamin B12 absorption. This condition predisposes individuals not only to gastric carcinoma but also to nutritional deficiencies such as pernicious anemia.
Other Potential Complications
While primarily associated with gastrointestinal disease, H. pylori infection has been investigated in relation to several extra-gastric conditions, including iron-deficiency anemia, idiopathic thrombocytopenic purpura, and growth retardation in children. Although causal links remain under study, eradication of the infection has been shown in some cases to improve these disorders, suggesting a broader systemic impact.
Asymptomatic Infections
Despite its pathogenic potential, a large proportion of H. pylori infections are asymptomatic. Many individuals harbor the bacterium without experiencing overt digestive symptoms or clinically significant gastric inflammation. Asymptomatic carriage is especially common in children and in populations with high prevalence rates, often exceeding 50% in some regions. Although these individuals may remain symptom-free for years, they remain at risk of developing complications later in life. Moreover, asymptomatic carriers contribute to ongoing transmission within households and communities through oral–oral or fecal–oral routes.
Diagnosis of Helicobacter pylori Infection
Accurate diagnosis relies on a combination of tests tailored to the patient’s condition. Both non-invasive and invasive methods are employed to detect the presence of H. pylori. Differentiating this infection from other gastric conditions is critical for proper management.
Non-Invasive Diagnostic Tests
Non-invasive tests are generally preferred as first-line diagnostic tools due to their ease of administration, safety, and high accuracy. Among these, the urea breath test (UBT) is considered the gold standard for non-invasive diagnosis. This test is based on the principle that H. pylori produces urease, an enzyme that breaks down urea into carbon dioxide and ammonia. During the procedure, patients ingest urea labeled with a stable or radioactive carbon isotope, and the exhaled breath is subsequently analyzed for isotopically labeled carbon dioxide. A positive result indicates active infection, and the test is highly sensitive and specific when performed correctly.
Another widely used non-invasive test is the stool antigen test (SAT), which detects H. pylori antigens present in feces. The test is suitable both for initial diagnosis and for confirming eradication following treatment. When performed with validated monoclonal antibody-based kits, its sensitivity and specificity are comparable to those of the urea breath test. Unlike serological methods, the SAT can distinguish between active and past infection, making it a valuable tool for monitoring treatment success.
Serological testing, which identifies antibodies against H. pylori in the blood, has historically been used for diagnostic purposes but is now less favored in clinical practice. The main limitation of serology is its inability to distinguish between active and previous infection, as antibodies may persist long after eradication. Consequently, serology is primarily employed in epidemiological studies and population-level surveys, rather than in routine clinical diagnosis.
Invasive Diagnostic Techniques
Invasive tests require upper gastrointestinal endoscopy and are typically reserved for patients in whom endoscopy is indicated for clinical reasons, such as evaluation of gastric ulcers, upper gastrointestinal bleeding, or suspicion of malignancy. During endoscopy, biopsy specimens are collected from the gastric mucosa and analyzed through a variety of methods.
Histological examination remains one of the most informative techniques. Tissue samples are stained with special dyes and examined under a microscope, allowing for the direct visualization of H. pylori as well as assessment of the extent of mucosal inflammation, atrophy, or intestinal metaplasia. Histology is highly sensitive and specific, though accuracy can be affected by sampling errors or prior use of antibiotics and proton pump inhibitors.
The rapid urease test (RUT) is another biopsy-based diagnostic tool that detects urease activity directly within gastric tissue. Biopsy samples are placed in a medium containing urea and a pH-sensitive indicator; a color change indicates the presence of urease-producing organisms. This method provides results within hours, offering clinicians rapid confirmation of infection. While highly specific, the test’s sensitivity can be reduced in patients who have recently taken antibiotics or acid-suppressive therapy.
Culture of gastric biopsy specimens provides the most definitive diagnosis and enables antibiotic susceptibility testing. This method is technically demanding, requires specialized laboratory facilities, and is less commonly performed in routine clinical settings. However, culture remains invaluable in cases of treatment failure or suspected antibiotic resistance, as it allows clinicians to tailor therapy based on the bacterium’s resistance profile.
Differential Diagnosis
Because H. pylori infection shares clinical and histological features with a number of other gastric conditions, differential diagnosis is an important aspect of evaluation. Gastric and duodenal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) can closely mimic ulcers associated with H. pylori, necessitating careful assessment. Gastric malignancies, including adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma, may also present with similar symptoms and require exclusion through endoscopy and histopathological evaluation.
Other conditions that may resemble H. pylori gastritis include autoimmune gastritis, in which immune-mediated destruction of parietal cells produces mucosal changes that can be mistaken for infection. Functional dyspepsia, a condition characterized by chronic indigestion without identifiable structural cause, and non-infectious forms of gastritis, such as those induced by alcohol, bile reflux, or chemical irritation, also fall within the differential diagnosis.
Confirming H. pylori infection before initiating treatment is considered standard clinical practice. Empirical therapy without diagnosis is discouraged, as it risks unnecessary antibiotic use, promotes resistance, and exposes patients to avoidable side effects. Selection of an appropriate test depends on factors such as availability, cost, and whether the patient requires endoscopy for other diagnostic reasons. In all cases, accurate diagnosis is the foundation of effective management and contributes to the long-term prevention of complications such as recurrent ulcers and gastric carcinoma.
Treatment and Management
The treatment of Helicobacter pylori infection involves specific antibiotic combinations, supportive therapies to enhance eradication, and strategies to overcome common obstacles such as resistance. Effective management requires choosing appropriate medications based on local resistance patterns and patient history.
Antibiotic Regimens
Antibiotic therapy is the primary means of H. pylori eradication. Monotherapy is ineffective due to rapid emergence of resistance; therefore, multi-drug regimens are employed. Proton pump inhibitors (PPIs) are consistently included to suppress gastric acid, which enhances the stability and efficacy of antibiotics. The most common regimens include:
- Triple Therapy: Traditional first-line treatment, known as triple therapy, involves a PPI combined with clarithromycin and either amoxicillin or metronidazole. Standard duration is 10 to 14 days, with a 14-day course generally yielding higher eradication rates. However, the effectiveness of triple therapy has declined in many regions due to rising clarithromycin resistance, with eradication rates sometimes falling below 70%.
- Quadruple Therapy: Bismuth-based quadruple therapy includes a PPI, bismuth subsalicylate or subcitrate, tetracycline, and metronidazole. This regimen is particularly effective in areas where clarithromycin resistance is prevalent or in cases of prior treatment failure. Duration is typically 10 to 14 days.
- Non-Bismuth Quadruple Therapy (Concomitant Therapy): An alternative to bismuth-containing regimens is non-bismuth quadruple therapy, which combines a PPI with clarithromycin, amoxicillin, and metronidazole or tinidazole. This regimen is increasingly recommended in regions with intermediate resistance levels.
- Sequential and Hybrid Therapies: Sequential therapy involves initial administration of a PPI and amoxicillin for 5 days, followed by a PPI, clarithromycin, and metronidazole for another 5 days. Hybrid therapy combines elements of sequential and concomitant regimens, beginning with PPI and amoxicillin for 7 days and then adding clarithromycin and metronidazole for another 7 days. These approaches have shown improved eradication rates in some populations.
- Rescue and Salvage Therapies: When initial regimens fail, second-line or salvage therapies are employed, often guided by antimicrobial susceptibility testing. Options include levofloxacin-based triple therapy or rifabutin-containing regimens. Tailored treatment based on antibiotic sensitivity testing is increasingly recognized as the most effective approach for persistent infection.
Adjunctive Therapies
Adjunctive therapies aim to improve eradication rates and minimize treatment-related complications.
- Proton Pump Inhibitors (PPIs): Essential in nearly all regimens, PPIs reduce gastric acidity, providing a more favorable environment for antibiotic activity and enhancing mucosal healing. Potent PPIs or newer agents such as vonoprazan (a potassium-competitive acid blocker) may further improve outcomes.
- Bismuth Compounds: Possess direct antimicrobial activity against H. pylori and contribute to mucosal protection. When included in quadruple therapy, they significantly enhance eradication rates.
- Probiotics: Supplementation with specific strains, such as Lactobacillus or Saccharomyces boulardii, has been associated with reduced antibiotic-associated diarrhea and improved eradication rates, although their use is not universally standardized.
- Lifestyle Modifications: Avoidance of tobacco, excessive alcohol intake, and non-steroidal anti-inflammatory drugs (NSAIDs) can support gastric healing and reduce recurrence.
Treatment Challenges
Antibiotic resistance is the main challenge in managing H. pylori infection and varies by region. Clarithromycin resistance is particularly problematic, leading to marked reductions in triple therapy efficacy. Resistance to metronidazole and levofloxacin is also increasing globally, complicating the choice of salvage regimens.
Patient adherence is another critical factor, as complex multi-drug regimens with gastrointestinal side effects often result in premature discontinuation. Incomplete treatment not only reduces individual success rates but also contributes to the broader problem of resistance.
Verification of eradication is considered standard practice. Non-invasive tests such as the urea breath test or stool antigen test are recommended at least four weeks after completion of therapy and at least two weeks after discontinuation of PPIs to ensure accuracy. Endoscopic biopsy with histology or culture may be used in selected cases.
Retreatment often involves alternative antibiotic combinations guided by susceptibility testing to overcome resistance.
Prevention and Control Strategies
Effective prevention of Helicobacter pylori infection involves coordinated efforts at both community and individual levels.
Personal Hygiene Practices
Individual hygiene habits significantly impact H. pylori infection risk.
- Regular handwashing with soap and clean water before meals and after using the restroom is one of the most effective methods to minimize accidental ingestion of the bacteria.
- Avoiding the sharing of eating utensils, cups, and drinking bottles reduces the chance of person-to-person transmission, particularly in crowded households or communal living environments.
- Maintaining good oral hygiene, including brushing teeth at least twice daily and using clean toothbrushes, may help limit bacterial colonization in the mouth and reduce oral reservoirs of infection.
- Safe food handling is essential, and individuals should thoroughly wash raw fruits and vegetables before consumption to prevent contamination with fecal matter carrying H. pylori.
- Proper cooking of meat and other animal products lowers the likelihood of ingesting viable bacteria that may survive in undercooked food.
- Access to safe drinking water is vital, as contaminated water has been implicated in the spread of H. pylori in endemic areas.
Antibiotic Resistance in Helicobacter pylori
Antibiotic resistance in Helicobacter pylori has become a significant barrier to effective eradication.
Prevalence of Resistance
Resistance to clarithromycin, one of the most widely used drugs in first-line triple therapy, ranges from 10% in some regions to over 30% in others, particularly in Europe and parts of Asia. Such high levels of resistance have severely reduced the efficacy of clarithromycin-based regimens, often rendering them unsuitable as empirical treatment. Metronidazole resistance is even more widespread, with rates exceeding 40% in many developing countries where the drug is frequently used for parasitic and gynecological infections. This resistance often contributes to treatment failure when metronidazole-based combinations are prescribed.
Resistance to fluoroquinolones, especially levofloxacin, has also increased as these drugs are increasingly used in second-line or rescue therapies. Rising resistance rates now compromise the utility of levofloxacin-containing regimens in some populations. By contrast, amoxicillin and tetracycline resistance remain relatively low on a global scale; however, emerging reports from certain regions indicate that these rates are gradually increasing, raising concerns for future treatment options. The underlying mechanisms of resistance typically involve point mutations in bacterial DNA, particularly in genes encoding ribosomal RNA or target enzymes, which prevent effective antibiotic binding or reduce drug uptake.
Strategies to Overcome Resistance
The growing challenge of resistance has prompted the development of new therapeutic approaches. Tailored therapy based on antibiotic susceptibility testing provides the highest eradication rates, as treatment can be adjusted to match the resistance profile of the infecting strain. In regions where testing is unavailable, clinicians often rely on population-level surveillance data to guide empirical choices. In areas with high clarithromycin resistance, bismuth quadruple therapy—combining a proton pump inhibitor, bismuth, tetracycline, and metronidazole—has become the preferred first-line regimen. Concomitant therapy, which uses a combination of clarithromycin, amoxicillin, metronidazole, and a proton pump inhibitor, also offers improved eradication rates in such settings.
Newer therapeutic strategies include rifabutin-based regimens, which are increasingly used as rescue therapies after multiple eradication failures. Other novel drug combinations and adjunctive therapies, such as probiotics, are being investigated to improve treatment tolerability and reduce the likelihood of recurrence. Importantly, patient adherence to prescribed regimens remains critical to successful eradication, as incomplete or inconsistent use of antibiotics increases the risk of treatment failure and further resistance development. On a broader scale, rational antibiotic stewardship—avoiding unnecessary or inappropriate antibiotic use—is essential to slow the emergence of resistant strains.
Helicobacter pylori and Gastric Cancer
Helicobacter pylori infection is recognized as a major risk factor for the development of gastric cancer, particularly non-cardia gastric adenocarcinoma. The World Health Organization classifies H. pylori as a Group I carcinogen, reflecting its established role in gastric carcinogenesis. The bacterium contributes to cancer formation through long-term colonization of the stomach lining, chronic inflammation, and the action of specific virulence factors.
Carcinogenic Mechanisms
The progression from Helicobacter pylori infection to gastric cancer is gradual and follows a well-recognized sequence of pathological changes known as the Correa cascade. Persistent infection initially produces chronic gastritis, an ongoing inflammation of the stomach lining. If the infection is not resolved, the inflammation may lead to atrophic gastritis, in which gastric glands are progressively lost and the mucosal layer becomes thinner. Over time, some areas of the stomach lining may undergo intestinal metaplasia, a transformation in which the gastric epithelium takes on characteristics of intestinal tissue. This stage can further progress to dysplasia, a precancerous condition characterized by abnormal cellular growth and disorganization. Ultimately, in a subset of individuals, these changes culminate in the development of gastric adenocarcinoma.
Several bacterial and host factors contribute to this carcinogenic process. Among the most important are bacterial virulence factors. The cytotoxin-associated gene A (CagA) protein is injected into gastric epithelial cells through a type IV secretion system. Once inside the cell, CagA disrupts normal signaling pathways, leading to abnormal cell proliferation and an increased risk of oncogenesis. Another important virulence factor, the vacuolating cytotoxin A (VacA), induces cellular injury by creating vacuoles within epithelial cells, triggering apoptosis, and interfering with immune regulation.
In addition to direct toxin effects, chronic infection produces persistent inflammation and oxidative stress. Activated immune cells release reactive oxygen and nitrogen species, which damage DNA and increase the likelihood of mutations in gastric epithelial cells. Epigenetic alterations also play a role: H. pylori infection has been associated with abnormal DNA methylation and the silencing of tumor suppressor genes, further promoting malignant transformation. Host genetic susceptibility adds another layer of complexity, with polymorphisms in immune response genes, such as interleukins, influencing the severity of inflammation and the risk of cancer progression.
It is important to note that not all individuals infected with H. pylori develop gastric cancer. The likelihood of malignancy depends on a combination of factors, including the virulence of the infecting bacterial strain, the host’s genetic background, and environmental exposures such as high-salt diets, smoking, and alcohol use.