For a long time, people believed acidity and gastric ulcers were caused by stress and lifestyle. However, in 1980s, two Australian scientists observed that most people with acidity had a spiral shaped bacteria in their stomachs.
The stomach is a very acidic environment, and at first, it was hard to believe any organism can survive in it. By ingesting the bacteria themselves, and through repeated experiments, they were able to prove that the leading cause of acidity was Helicobacter Pylori, bacteria that live in almost half of people without showing any symptoms.
H. Pylori is a spiral-shaped bacterium that lives on the stomach lining. High mobility, and the ability to convert urea into ammonia, allow it to survive in the highly acidic environment of the stomach (1).
Shaped as rods of 2-4 micrometers in length and 0.5-1 micrometers in width, it has unique identifying features of 2-6 rod-like flagella (see image above). These are about 3 micrometers in length, with a very distinctive bulb at the end.
There are several species of Helicobacter. However, Helicobacter pylori is specific to the human stomach. Different Helicobacter species have also been found in cats, dogs and other animals where they are known to cause ulcers.
H. pylori strongly adapts to our unique stomach environments allowing it to stay throughout our lives. This is one reason why infections acquired during childhood continue in adults.
The pH of stomach lining varies between 4 and 6.5. But the bacterium prefers to grow around a pH of 5.5. It survives the fluctuations in stomach acidity by converting urea in the stomach into ammonia and bicarbonates. And by quickly moving away from high acidic regions.
This unique ability to digest urea is a hallmark of H. pylori, and is frequently used for confirming the bacterial infection.
Prevalence (approximate data from 2013-14) (2):
US and Canada: 30-35%
Western Europe: 30-70%
Eastern Europe: 40-80%
India and China: 60%
Prevalence in younger generation is lower, e.g., in China the numbers were 30% in children compared to almost 60% in adults (2).
For past several decades, there is a steady decline in cases due to better hygiene & other unknown reasons. As an example, in The Netherlands, cases declined from 48% in 1940s to 16% in 1980s (2).
In developing countries, the infections often start in children and continue as they grow into adults, causing acidity, ulcers and stomach cancers. However, in developed countries most cases are observed among adults. First and second-generation immigrants from developing countries have higher rates compared to natives, likely from infections acquired during childhood.
How H. pylori transmits is not completely understood; however, with high probability, children acquire it during early childhood.
Most likely medium of transmission among people is either oral through saliva or fecal or both.
The bacterium has been detected in saliva, vomit, gastric reflux and feces.
There are no data to support infection from dentists, nurses, clinic visits for sexually-transmitted-disease or gastroenterologists (3).
There are many risk factors for infection:
Family members: 75% of spouses and parents of children and half of siblings have been found to be in positive for those infected (4).
Age: About one-third of children and adults under 30 years of age have been found infected but the numbers increase to almost two-third among the 55-65 age groups (5).
Race: Risk of infection among African Americans and Hispanic groups is twice that among Europeans (6).
Living conditions: Risk increases among those sharing beds and living in crowded homes. That's because close proximity increases the oral or fecal transmission of the pylori bacteria. Those in rural communities seem to have higher prevalence than in urban communities (7).
Others: Risk has been found to be higher in US for those in lower socio-economic backgrounds, poor living conditions. People recently immigrated from regions with higher prevalence (e.g., developing or tropical countries) also tend to be at higher risk.
No difference was found between genders. The impact of smoking and alcohol is also not clearly understood (7).
There might be some genetic component that is not yet fully understood. Studies of identical twins growing apart often show similar infections (8).
Risk increases with additional common symptoms of:
Difficult in swallowing (dysphagia)
Family history of abnormal and excessive tissue growth (neoplasm)
Helicobacter pylori is a known carcinogen (9). Although extremely rare, studies have shown that it can cause cancer of the duodenum (end of stomach that connects to the small intestine ).
Infections are often asymptotic but in serious cases, they can cause high acidity, ulcers, and acid reflex which can be very difficult to diagnose.
Infection generally has no immediate implications unless it results in common symptoms of gastric ulcer or other annoying side effects.
There are no clear data to indicate H. pylori increases the risk of GERD or heart burn (1).
The risk of developing gastric cancer due to H. pylori in US and Europe is relatively small (1-2% cases). However, the bacterial infection increases the risk ten-fold and treatment seem to have no change in this risk (1).
There are different kinds of H. pylori test:
Urea breath test (10): when the bacteria convert carbon-labeled urea into ammonia & CO2. These can be detected through a breath test. The test is highly reliable, at about 95% sensitivity and specificity (true positive and true negative rates, respectively). The cost is much higher at 4-5 times of fecal antigen test.
Fecal antigen test: an ELISA test that checks for the presence of bacteria in stool. It has approx. 95% sensitivity and specificity.
Blood antibody test: checks for IgG antibodies in the blood, from current or past infections. It does not depend on medication or antibiotics. It is an efficient way to check large groups for population-based studies.
Advantage: Simple and easy test with a finger prick sample that can be collected at home and mailed to the lab from home. It does not depend on medication (e.g., PPIs) or antibiotics.
Limitation: can't tell whether it's currently active or a past infection. Therefore a positive case might require another stool or urea breath test for confirmation.
Things to Keep in Mind:
An IgG antibody test checks for immune response against the infection. However, very recent infections might not have produced enough antibodies to detect. And very old infections might have very little antibodies left in the blood. Some people may not even produce enough antibodies.
For taking the stool test, one should not be taking acid reducing medications (PPIs or proton-pump inhibitors such as Nexium, Prilosec, Omeprazole, Esomeprazole, Protonix) for at least two weeks. And they should not be on antibiotics for at least 4 weeks. The blood antibody test has no such requirement.
A triple therapy of PPI (Omeprazole, Esomeprazole, Nexium or Prilosec) and antibiotics (amoxycillin and levofloxacin or clarithromycin or bismuth-containing quadruple regimen) for 7-14 days is a prescribed testing methodology (11).
Probiotics have shown to help with better outcomes in treatment (12).
Mayo Clinic recommends all treatment regimens should be taken for 14 days, and eradication testing should be performed in all patients (13).
The reinfection rate is relatively low, at around 1-3%, mainly in cases where the bacteria is not fully removed from the body. But reinfection rates vary by regions, with some countries showing much higher rates of reinfection.
Definition: Just as our body develops immunity against bacteria and viruses over time, these pathogens have clever defense mechanisms to counteract and overcome our body's defense mechanisms. They carry 'virulence' genes that are capable of producing molecules that allow them to enter the body, hide without detection, and then multiply and grow to cause infections (14). In that sense, 'virulence factors' are genes that allow the bacterial 'wolfs' to wrap themselves in the 'sheep's clothing' of our body's cells (15).
Some of these protein molecules are more dangerous than others. For H. pylori, certain strains or variations of the bacteria are more infectious. Few of them are listed here (1):
cagA: this gene produces protein CagA (also called cytotoxin-associated gene A) and is found more often than others genes. About 50-70% of all strains in US and Europe are cagA. Its presence causes more severe infection, stronger gastritis (acidity), higher inflammation and greater risk of stomach ulcer and gastric cancer.
vacA: vacuolating toxin A—which causes holes-like features in the cells—about half of strains carry vacA. This gene increases the risk of damage to the lining of the stomach. VacA carrying strains also have much higher adaptability. This allows a more persistent infection, observed as a constant growing and shrinking duodenal ulcer.
babA: blood-group antigen binding adhesion, is known to increase the risk of peptic ulcer and gastric cancer. It is often a more severe disease and long-term infection.
dupA: duodenal-ulcer promoting gene A. It is associated with ulcer in the duodenum (the part of stomach connecting with small intestine). But known for reduced risk of damage to lining of the stomach.
iceA: induced-by-contact-with-epithelium A, a gene causing higher inflammation. In some instances it even causes peptic ulcer.
oipA: outer-membrane inflammatory protein A gene, is often linked to cagA. It is known to cause duodenal ulcer and gastric cancer.
virB and virD are part of the cagA pathogenicity island (PAI—the gene clusters of pathogens responsible for causing the disease). They increase the risk of peptic ulcer and gastric cancer.
To Barry J. Marshall and J. Robin Warren for their discovery of “the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease".
Source: The Nobel Prize.
Johannes G. Kusters, Arnoud H. M. van Vliet, and Ernst J. Kuipers, The Pathogenesis of Helicobacter pylori Infection, Clin Microbiol Rev. 2006 Jul; 19(3): 449–490.
Dulciene Maria Magalhães Queiroz Francesco Luzza, Epidemiology of Helicobacter pylori Infection, Helicobacter, Vol 11 (1), Oct 2006.
F. Mégraud, Transmission of Helicobacter pylori: faecal-oral versus oral-oral route, Aliment Pharmacol Ther. 1995;9 Suppl 2:85-91.
Yavuz Selim Sari et. al., H pylori: Treatment for the patient only or the whole family? World J Gastroenterol. 2008 Feb 28; 14(8): 1244–1247.
P. M. Webb et. al., Relation between infection with Helicobacter pylori and living conditions in childhood: evidence for person to person transmission in early life, BMJ, 1994 Mar 19; 308(6931):750-3.
James E. Everhart et. al., Seroprevalence and Ethnic Differences in Helicobacter pylori Infection among Adults in the United States, The Journal of Infectious Diseases, Volume 181, Issue 4, April 2000, Pages 1359–1363.
Leonardo H. Eusebi, Rocco M. Zagari and Franco Bazzoli, Epidemiology of Helicobacter pylori Infection, Helicobacter 19 (Suppl. 1): 1–5.
H. M. Malaty, L. Engstrand, N. L. Pedersen, and D. Y. Graham, Helicobacter pylori infection: genetic and environmental influences. A study of twins, Ann Intern Med 94 Jun 15;120(12):982-6.
The Nobel Prize: https://www.nobelprize.org/prizes/medicine/2005/press-release/.
Chiara Ricci, John Holton, and Dino Vaira, Diagnosis of Helicobacter pylori: invasive and non-invasive tests, Best Pract Res Clin Gastroenterol. 2007; 21(2):299-313.
William D Chey, Benjamin C Y Wong, American College of Gastroenterology guideline on the management of Helicobacter pylori infection, Am J Gastroenterol. 2007 Aug;102(8):1808-25.
Goran Hauser, Nermin Salkic, Karina Vukelic, Alenka JajacKnez, Davor Stimac, Probiotics for standard triple Helicobacter pylori eradication: a randomized, double-blind, placebo-controlled trial, Randomized Controlled Trial, Medicine (Baltimore) 2015 May; 94(17):e685.
Amrit K. Kamboj, Thomas G. Cotter, and Amy S. Oxentenko, Helicobacter pylori: The Past, Present, and Future in Management, Mayo Clin Proc. April 2017; 92(4):599-604.
Steven AR Webb and Charlene M Kahler, Bench-to-bedside review: Bacterial virulence and subversion of host defences, Critical Care, Volume 12, Article number: 234 (2008).
Alan S Cross, What is a virulence factor? Crit Care. 2008; 12(6): 196.
Jennifer M. Yeh, Chin Hur, Deb Schrag, Karen M. Kuntz, Majid Ezzati, Natasha Stout, Zachary Ward, Sue J. Goldie, Contribution of H. pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model, PLoS Medicine, 2013, 10(5):e1001451.
Jennifer M. Yeh, Sue J. Goldie, Karen M. Kuntz, and Majid Ezzati, Effects of Helicobacter pylori infection and smoking on gastric cancer incidence in China: a population-level analysis of trends and projections, Cancer Causes Control. 2009 Dec; 20(10): 2021–2029.
Chaochen Wang, Takeshi Nishiyama, Shogo Kikuchi, Manami Inoue, Norie Sawada, Shoichiro Tsugane & Yingsong Lin, Changing trends in the prevalence of H. pylori infection in Japan (1908–2003): a systematic review and meta-regression analysis of 170,752 individuals, Scientific Reports Vol 7, 15491 (2017).