Helicobacter pylori (H. pylori) is a type of bacteria that causes infection in the stomach. It is the main cause of peptic ulcers, and it can also cause gastritis and stomach cancer.

About 30 to 40 percent of people in the United States get an H. pylori infection. Most people get it as a child. H. pylori usually does not cause symptoms. But it can break down the inner protective coating in some people's stomachs and cause inflammation. This can lead to gastritis or a peptic ulcer.

Researchers aren't sure how H. pylori spreads. They think that it may spread by unclean food and water, or through contact with an infected person's saliva and other body fluids.

A peptic ulcer causes a dull or burning pain in your stomach, especially when you have an empty stomach. It lasts for minutes to hours, and it may come and go for several days or weeks. It may also cause other symptoms, such as bloating, nausea, and weight loss. If you have the symptoms of a peptic ulcer, your health care provider will check to see whether you have H. pylori. There are blood, breath, and stool tests to check for H. pylori. In some cases, you may need an upper endoscopy, often with a biopsy.

If you do have a peptic ulcer, the treatment is with a combination of antibiotics and acid-reducing medicines. You will need to be tested again after treatment to make sure the infection is gone.

There is no vaccine for H. pylori. Since H. pylori might spread through unclean food and water, you might be able to prevent it if you

• Wash your hands after using the bathroom and before eating
• Eat properly prepared food
• Drink water from a clean, safe source

A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus CAMPYLOBACTER, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus HELICOBACTER. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405).

To cause disease, a pathogen must successfully achieve four steps or stages of pathogenesis: exposure (contact), adhesion (colonization), invasion, and infection.

Once adhesion is successful, invasion can proceed. Invasion involves the dissemination of a pathogen throughout local tissues or the body. Pathogens may produce exoenzymes or toxins, which serve as virulence factors that allow them to colonize and damage host tissues as they spread deeper into the body. Pathogens may also produce virulence factors that protect them against immune system defenses. A pathogen’s specific virulence factors determine the degree of tissue damage that occurs. Figure below shows the invasion of H. pylori into the tissues of the stomach, causing damage as it progresses.

H. pylori is able to invade the lining of the stomach by producing virulence factors that enable it pass through the mucin layer covering epithelial cells. (credit: modification of work by Zina Deretsky, National Science Foundation)

Intracellular pathogens achieve invasion by entering the host’s cells and reproducing. Some are obligate intracellular pathogens (meaning they can only reproduce inside of host cells) and others are facultative intracellular pathogens (meaning they can reproduce either inside or outside of host cells). By entering the host cells, intracellular pathogens are able to evade some mechanisms of the immune system while also exploiting the nutrients in the host cell.

Entry to a cell can occur by endocytosis. For most kinds of host cells, pathogens use one of two different mechanisms for endocytosis and entry. One mechanism relies on effector proteins secreted by the pathogen; these effector proteins trigger entry into the host cell. This is the method that Salmonella and Shigella use when invading intestinal epithelial cells. When these pathogens come in contact with epithelial cells in the intestine, they secrete effector molecules that cause protrusions of membrane ruffles that bring the bacterial cell in. This process is called membrane ruffling. The second mechanism relies on surface proteins expressed on the pathogen that bind to receptors on the host cell, resulting in entry. For example, Yersiniapseudotuberculosis produces a surface protein known as invasin that binds to beta-1 integrins expressed on the surface of host cells.

Some host cells, such as white blood cells and other phagocytes of the immune system, actively endocytose pathogens in a process called phagocytosis. Although phagocytosis allows the pathogen to gain entry to the host cell, in most cases, the host cell kills and degrades the pathogen by using digestive enzymes. Normally, when a pathogen is ingested by a phagocyte, it is enclosed within a phagosome in the cytoplasm; the phagosome fuses with a lysosome to form a phagolysosome, where digestive enzymes kill the pathogen. However, some intracellular pathogens have the ability to survive and multiply within phagocytes. Examples include Listeria monocytogenes and Shigella; these bacteria produce proteins that lyse the phagosome before it fuses with the lysosome, allowing the bacteria to escape into the phagocyte’s cytoplasm where they can multiply. Bacteria such as Mycobacterium tuberculosis, Legionella pneumophila, and Salmonella species use a slightly different mechanism to evade being digested by the phagocyte. These bacteria prevent the fusion of the phagosome with the lysosome, thus remaining alive and dividing within the phagosome.

The mucosa of the stomach is exposed to the highly corrosive acidity of gastric juice. Gastric enzymes that can digest protein can also digest the stomach itself. The stomach is protected from self-digestion by the mucosal barrier. This barrier has several components. First, the stomach wall is covered by a thick coating of bicarbonate-rich mucus. This mucus forms a physical barrier, and its bicarbonate ions neutralize acid. Second, the epithelial cells of the stomach's mucosa meet at tight junctions, which block gastric juice from penetrating the underlying tissue layers. Finally, stem cells located where gastric glands join the gastric pits quickly replace damaged epithelial mucosal cells, when the epithelial cells are shed. In fact, the surface epithelium of the stomach is completely replaced every 3 to 6 days.

HOMEOSTATIC IMBALANCES

Ulcers: When the Mucosal Barrier Breaks Down

As effective as the mucosal barrier is, it is not a “fail-safe” mechanism. Sometimes, gastric juice eats away at the superficial lining of the stomach mucosa, creating erosions, which mostly heal on their own. Deeper and larger erosions are called ulcers.

Why does the mucosal barrier break down? A number of factors can interfere with its ability to protect the stomach lining. The majority of all ulcers are caused by either excessive intake of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or Helicobacter pylori infection.

Antacids help relieve symptoms of ulcers such as “burning” pain and indigestion. When ulcers are caused by NSAID use, switching to other classes of pain relievers allows healing. When caused by H. pylori infection, antibiotics are effective.

A potential complication of ulcers is perforation: Perforated ulcers create a hole in the stomach wall, resulting in peritonitis (inflammation of the peritoneum). These ulcers must be repaired surgically.

The gram-negative bacterium Helicobacter pylori is able to tolerate the acidic environment of the human stomach and has been shown to be a major cause of peptic ulcers, which are ulcers of the stomach or duodenum. The bacterium is also associated with increased risk of stomach cancer (Figure). According to the CDC, approximately two-thirds of the population is infected with H. pylori, but less than 20% have a risk of developing ulcers or stomach cancer. H. pylori is found in approximately 80% of stomach ulcers and in over 90% of duodenal ulcers.

H. pylori colonizes epithelial cells in the stomach using pili for adhesion. These bacteria produce urease, which stimulates an immune response and creates ammonia that neutralizes stomach acids to provide a more hospitable microenvironment. The infection damages the cells of the stomach lining, including those that normally produce the protective mucus that serves as a barrier between the tissue and stomach acid. As a result, inflammation (gastritis) occurs and ulcers may slowly develop. Ulcer formation can also be caused by toxin activity. It has been reported that 50% of clinical isolates of H. pylori have detectable levels of exotoxin activity in vitro. This toxin, VacA, induces vacuole formation in host cells. VacA has no primary sequence homology with other bacterial toxins, and in a mouse model, there is a correlation between the presence of the toxin gene, the activity of the toxin, and gastric epithelial tissue damage.

Signs and symptoms include nausea, lack of appetite, bloating, burping, and weight loss. Bleeding ulcers may produce dark stools. If no treatment is provided, the ulcers can become deeper, more tissues can be involved, and stomach perforation can occur. Because perforation allows digestive enzymes and acid to leak into the body, it is a very serious condition.

Helicobacter infection decreases mucus production and causes peptic ulcers. (credit top left photo: modification of work by "Santhosh Thomas"/YouTube; credit top right photo: modification of work by Moriya M, Uehara A, Okumura T, Miyamoto M, and Kohgo Y)

To diagnose H. pylori infection, multiple methods are available. In a breath test, the patient swallows radiolabeled urea. If H. pylori is present, the bacteria will produce urease to break down the urea. This reaction produces radiolabeled carbon dioxide that can be detected in the patient’s breath. Blood testing can also be used to detect antibodies to H. pylori. The bacteria themselves can be detected using either a stool test or a stomach wall biopsy.

Antibiotics can be used to treat the infection. However, unique to H. pylori, the recommendation from the US Food and Drug Administration is to use a triple therapy. The current protocols are 10 days of treatment with omeprazole, amoxicillin, and clarithromycin (OAC); 14 days of treatment with bismuth subsalicylate, metronidazole, and tetracycline (BMT); or 10 or 14 days of treatment with lansoprazole, amoxicillin, and clarithromycin (LAC). Omeprazole, bismuth subsalicylate, and lansoprazole are not antibiotics but are instead used to decrease acid levels because H. pylori prefers acidic environments.

Although treatment is often valuable, there are also risks to H. pylori eradication. Infection with H. pylori may actually protect against some cancers, such as esophageal adenocarcinoma and gastroesophageal reflux disease.

Your stomach lining has an important job. It makes acid and enzymes that help break down food so you can extract the nutrients you need. The lining also protects itself from acid damage by secreting mucus. But sometimes the lining gets inflamed and starts making less acid, enzymes and mucus. This type of inflammation is called gastritis, and it can cause long-term problems.

Some people think they have gastritis when they have pain or an uncomfortable feeling in their upper stomach. But many other conditions can cause these symptoms. Gastritis can sometimes lead to pain, nausea and vomiting. But it often has no symptoms at all. If left untreated, though, some types of gastritis can lead to ulcers (sores in the stomach lining) or even stomach cancer.

People used to think gastritis and ulcers were caused by stress and spicy foods. But research studies show that bacteria called Helicobacter pylori are often to blame. Usually, these bacteria cause no symptoms. In the United States, 20% to 50% of the population may be infected with H. pylori.

H. pylori breaks down the inner protective coating in some people’s stomachs and causes inflammation. “I tell people H. pylori is like having termites in your stomach,” says Dr. David Graham, an expert in digestive diseases at Baylor College of Medicine in Texas. “You usually don’t know you have termites until someone tells you, and you ignore it at your own risk.” H. pylori can spread by passing from person to person or through contaminated food or water. Infections can be treated with bacteria-killing drugs called antibiotics.

One type of gastritis, called erosive gastritis, wears away the stomach lining. The most common cause of erosive gastritis is long-term use of medications called non-steroidal anti-inflammatory drugs. These include aspirin and ibuprofen. “When you stop taking the drugs, the condition usually goes away,” says Graham. Doctors might also recommend reducing the dose or switching to another class of pain medication.

Less common causes of gastritis include certain digestive disorders (such as Crohn’s disease) and autoimmune disorders, in which the body’s protective immune cells mistakenly attack healthy cells in the stomach lining.

Gastritis can be diagnosed with an endoscope, a thin tube with a tiny camera on the end, which is inserted through the patient’s mouth or nose and into the stomach. The doctor will look at the stomach lining and may also remove some tissue samples for testing. Treatment will depend on the type of gastritis you have.

Although stress and spicy foods don’t cause gastritis and ulcers, they can make symptoms worse. Milk might provide brief relief, but it also increases stomach acid, which can worsen symptoms. Your doctor may recommend taking antacids or other drugs to reduce acid in the stomach.

Talk with a health care provider if you’re concerned about ongoing pain or discomfort in your stomach. These symptoms can have many causes. Your doctor can help determine the best course of action for you.

Watch for Ulcers

Gastritis can lead to ulcers over time. Symptoms of ulcers include pain between the belly button and breastbone that:

• starts between meals or during the night
• briefly stops if you eat or take antacids
• lasts for minutes to hours
• comes and goes for several days or weeks

Contact your doctor right away if you have:

• sudden sharp stomach pain that doesn’t go away
• black or bloody stools
• vomit that is bloody or looks like coffee grounds

What is Helicobacter pylori?

Helicobacter pylori, or H. pylori, is a spiral-shaped bacterium that grows in the mucus layer that coats the inside of the human stomach.

To survive in the harsh, acidic environment of the stomach, H. pylori secretes an enzyme called urease, which converts the chemical urea to ammonia. The production of ammonia around H. pylori neutralizes the acidity of the stomach, making it more hospitable for the bacterium. In addition, the helical shape of H. pylori allows it to burrow into the mucus layer, which is less acidic than the inside space, or lumen, of the stomach. H. pylori can also attach to the cells that line the inner surface of the stomach.

Although immune cells that normally recognize and attack invading bacteria accumulate near sites of H. pylori infection, they are unable to reach the stomach lining. In addition, H. pylori has developed ways of interfering with local immune responses, making them ineffective in eliminating this bacterium.

H. pylori has coexisted with humans for many thousands of years, and infection with this bacterium is common. The Centers for Disease Control and Prevention (CDC) estimates that approximately two-thirds of the world’s population harbors the bacterium, with infection rates much higher in developing countries than in developed nations.

Although H. pylori infection does not cause illness in most infected people, it is a major risk factor for peptic ulcer disease and is responsible for the majority of ulcers of the stomach and upper small intestine. More information about H. pylori and peptic ulcer disease is available from the National Institute of Diabetes and Digestive and Kidney Diseases.

In 1994, the International Agency for Research on Cancer classified H. pylori as a carcinogen, or cancer-causing agent, in humans, despite conflicting results at the time. Since then, it has been increasingly accepted that colonization of the stomach with H. pylori is an important cause of gastric cancer and of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Infection with H. pylori is also associated with a reduced risk of esophageal adenocarcinoma.

H. pylori is thought to spread through contaminated food and water and through direct mouth-to-mouth contact. In most populations, the bacterium is first acquired during childhood. Infection is more likely in children living in poverty, in crowded conditions, and in areas with poor sanitation.

What is gastric cancer?

Gastric cancer, or cancer of the stomach, was once considered a single entity. Now, scientists divide this cancer into two main classes: gastric cardia cancer (cancer of the top inch of the stomach, where it meets the esophagus) and non-cardia gastric cancer (cancer in all other areas of the stomach).

Gastric cancer is the second most common cause of cancer-related deaths in the world, killing approximately 738,000 people in 2008. Gastric cancer is less common in the United States and other Western countries than in countries in Asia and South America.

Overall gastric cancer incidence is decreasing. However, this decline is mainly in the rates of non-cardia gastric cancer. Gastric cardia cancer, which was once very uncommon, has risen in incidence in recent decades.

Infection with H. pylori is the primary identified cause of gastric cancer. Other risk factors for gastric cancer include chronic gastritis; older age; male sex; a diet high in salted, smoked, or poorly preserved foods and low in fruits and vegetables; tobacco smoking; pernicious anemia; a history of stomach surgery for benign conditions; and a family history of stomach cancer.

H. pylori has different associations with the two main classes of gastric cancer. Whereas people infected with H. pylori have an increased risk of non-cardia gastric cancer, their risk of gastric cardia cancer is not increased and may even be decreased.

What evidence shows that H. pylori infection causes non-cardia gastric cancer?

Epidemiologic studies have shown that individuals infected with H. pylori have an increased risk of gastric adenocarcinoma. The risk increase appears to be restricted to non-cardia gastric cancer. For example, a 2001 combined analysis of 12 case–control studies of H. pylori and gastric cancer estimated that the risk of non-cardia gastric cancer was nearly six times higher for H. pylori-infected people than for uninfected people.

Additional evidence for an association between H. pylori infection and the risk of non-cardia gastric cancer comes from prospective cohort studies such as the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study in Finland. Comparing subjects who developed non-cardia gastric cancer with cancer-free control subjects, the researchers found that H. pylori-infected individuals had a nearly eightfold increased risk for non-cardia gastric cancer.

What is the evidence that H. pylori infection may reduce the risk of some cancers?

Several studies have detected an inverse relationship between H. pylori infection and gastric cardia cancer, although the evidence is not entirely consistent. The possibility of an inverse relationship between the bacterium and gastric cardia cancer is supported by the corresponding decrease in H. pylori infection rates in Western countries during the past century—the result of improved hygiene and widespread antibiotic use—and the increase in rates of gastric cardia cancer in these same regions.

Similar epidemiologic evidence suggests that H. pylori infection may be associated with a lower risk of esophageal adenocarcinoma. For example, a large case–control study in Sweden showed that the risk of esophageal adenocarcinoma in H. pylori-infected individuals was one-third that of uninfected individuals. A meta-analysis of 13 studies, including the Swedish study, found a 45 percent reduction in risk of esophageal adenocarcinoma with H. pylori infection. Moreover, as with gastric cardia cancer, dramatic increases in esophageal adenocarcinoma rates in several Western countries parallel the declines in H. pylori infection rates.

How might H. pylori infection decrease the risk of some cancers but increase the risk of other cancers?

Although it is not known for certain how H. pylori infection increases the risk of non-cardia gastric cancer, some researchers speculate that the long-term presence of an inflammatory response predisposes cells in the stomach lining to become cancerous. This idea is supported by the finding that increased expression of a single cytokine (interleukin-1-beta) in the stomach of transgenic mice causes sporadic gastric inflammation and cancer. The increased cell turnover resulting from ongoing cellular damage could increase the likelihood that cells will develop harmful mutations.

One hypothesis that may explain reduced risks of gastric cardia cancer and esophageal adenocarcinoma in H. pylori-infected individuals relates to the decline in stomach acidity that is often seen after decades of H. pylori colonization. This decline would reduce acid reflux into the esophagus, a major risk factor for adenocarcinomas affecting the upper stomach and esophagus.

What is cagA-positive H. pylori and how does it affect the risk of gastric and esophageal cancers?

Some H. pylori bacteria use a needle-like appendage to inject a toxin produced by a gene called cytotoxin-associated gene A (cagA) into the junctions where cells of the stomach lining meet. This toxin (known as CagA) alters the structure of stomach cells and allows the bacteria to attach to them more easily. Long-term exposure to the toxin causes chronic inflammation. However, not all strains of H. pylori carry the cagA gene; those that do are classified as cagA-positive.

Epidemiologic evidence suggests that infection with cagA-positive strains is especially associated with an increased risk of non-cardia gastric cancer and with reduced risks of gastric cardia cancer and esophageal adenocarcinoma. For example, a meta-analysis of 16 case–control studies conducted around the world showed that individuals infected with cagA-positive H. pylori had twice the risk of non-cardia gastric cancer than individuals infected with cagA-negative H. pylori. Conversely, a case–control study conducted in Sweden found that people infected with cagA-positive H. pylori had a statistically significantly reduced risk of esophageal adenocarcinoma. Similarly, another case–control study conducted in the United States found that infection with cagA-positive H. pylori was associated with a reduced risk of esophageal adenocarcinoma and gastric cardia cancer combined, but that infection with cagA-negative strains was not associated with risk.

Recent research has suggested a potential mechanism by which CagA could contribute to gastric carcinogenesis. In three studies, infection with CagA-positive H. pylori was associated with inactivation of tumor suppressor proteins, including p53.

What is gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and what is the evidence that it can be caused by H. pylori infection?

Gastric MALT lymphoma is a rare type of non-Hodgkin lymphoma that is characterized by the slow multiplication of B lymphocytes, a type of immune cell, in the stomach lining. This cancer represents approximately 12 percent of the extranodal (outside of lymph nodes) non-Hodgkin lymphoma that occurs among men and approximately 18 percent of extranodal non-Hodgkin lymphoma among women. During the period 1999–2003, the annual incidence of gastric MALT lymphoma in the United States was about one case for every 100,000 persons in the population.

Normally, the lining of the stomach lacks lymphoid (immune system) tissue, but development of this tissue is often stimulated in response to colonization of the lining by H. pylori. Only in rare cases does this tissue give rise to MALT lymphoma. However, nearly all patients with gastric MALT lymphoma show signs of H. pylori infection, and the risk of developing this tumor is more than six times higher in infected people than in uninfected people.

Is H. pylori infection associated with any other cancer?

Whether H. pylori infection is associated with risk of other cancers remains unclear. Some studies have found a possible association between H. pylori infection and pancreatic cancer, but the evidence is conflicting. Studies investigating the possibility that H. pylori is a risk factor for colorectal adenocarcinoma or lung cancer have found no evidence that it is associated with the risk of either type of cancer.

Can treatment to eradicate H. pylori infection reduce gastric cancer rates?

Long-term follow-up of data from a randomized clinical trial carried out in Shandong, China—an area where rates of gastric cancer are very high—found that short-term treatment with antibiotics to eradicate H. pylori reduced the incidence of gastric cancer. During a nearly 15-year period after treatment, gastric cancer incidence was reduced by almost 40 percent. When the results of this trial were pooled with those of several smaller trials examining the effects on gastric cancer incidence of antimicrobial treatment to eradicate H. pylori, a similar reduction was seen.

Who should seek diagnosis and treatment of an H. pylori infection?

According to the Centers for Disease Control and Prevention (CDC), people who have active gastric or duodenal ulcers or a documented history of ulcers should be tested for H. pylori, and, if they are infected, should be treated. Testing for and treating H. pylori infection is also recommended after resection of early gastric cancer and for low-grade gastric MALT lymphoma. However, most experts agree that the available evidence does not support widespread testing for and eradication of H. pylori infection.