An illustration of the the H. pylori pathogen, which is believed to have infected one out of every three humans.
Helicobacter pylori, a communicable bacterium, has existed for thousands of years. Its discovery, however, was made only four decades ago. Not only is its spread within the human population massive, but its effects can also be deadly. Now scientists and researchers in Manitoba are seeking new pathways toward diagnosing and treating a disease clouded by mystery and uncertainty.
In the vast microbial world that exists within our bodies, Helicobacter pylori is a remarkable and enigmatic bacterium. First described by medical scientists 40 years ago, Helicobacter pylori (or H. pylori) has captured the attention of researchers worldwide because of its unique properties and significant impacts on human health.
H. pylori infects an estimated one out of every two humans on Earth. In Canada, the rates are somewhat lower – about one in three (around 14 million) are believed to have the bacterium. Once infected, H. pylorioften goes unnoticed, as it does not cause symptoms in most infected individuals. However, for some, it can lead to various gastrointestinal disorders. A small but significant percentage of H. pylori infections will develop peptic ulcers or gastritis. Some will develop gastric cancer. Of those who contract cancer, about half will succumb to the disease.
Because H. pylori is so widespread and, at times, challenging to treat, researchers are turning to genomics to help identify better ways of diagnosing and understanding the bacterium in hopes of delivering more effective treatments. This spring, Genome Canada announced funding for a $1.6 million Helicobacter pylori Genomics Project, which Genome Prairie will administer.
Project research will be done at the National Microbiology Laboratory (NML) and the Cadham Provincial Laboratory in Winnipeg, Manitoba. The NML is part of the Public Health Agency of Canada and, since its establishment, includes a mandate to research infectious diseases, including, among others, bacterial pathogens, viral diseases, and zoonotic diseases (the NML famously played a crucial role in containing a west African Ebola outbreak in 2004. The Cadham Laboratory, meanwhile, is the main infectious disease research facility within the Government of Manitoba’s Ministry of Health (also known as Shared Health Manitoba).
At the NML, scientists and researchers provide ongoing diagnostic services to physicians and other healthcare experts across Canada, including laboratory diagnostic support requests to deal with H. pylori.
Aleisha Reimer, Chief of Innovation and Application Development Section within the Division of Enteric Diseases at the NML and the H. pylori Genomics Project receptor lead, said the laboratory receives constant diagnostic requests for H. pylori infections. A large portion of the requests to the NML, said Reimer, are made because no other diagnostic options are available in Canada.
“The NML is often the last stop in the diagnostic process. We still get weekly requests from specialists trying to find answers for their patients. I respond that we currently don’t have a validated test to provide the results they need,” said Reimer.
“In the end, we often provide a research-use-only test meaning the physician can’t use the results for diagnostic purposes, but it underscores just how often our requests come out of desperation.”
Currently, the most accurate way to diagnose an H. pylori infection involves endoscopy (a procedure to look inside the body) to visualize the stomach lining and obtain a biopsy for culture and antimicrobial resistance testing. Other methods, such as breath, stool, or blood tests, are less reliable and currently don’t allow for antimicrobial resistance testing.
“We’re trying to drag H. pylori testing into the 21st century,” said Dr. David Alexander, the H. pylori Genomic Project’s academic lead who is leading research at the Cadham Provincial Laboratory. Infectious diseases, including H. pylori, have long fascinated Alexander, whose involvement in this area of research extends back more than three decades. “We want to address the gaps in how H. pylori is diagnosed, and treatment decisions are made.”
Alexander, also an assistant professor at the Max Rady College of Medicine, noted that the current methods of diagnosing H. pylori have significant drawbacks, ranging from cost to complexity.
“The main test used is a serology test (drawing blood). Antibodies in the blood can only tell us that a patient was once infected, but they can’t detect present infections. Another is called the breath test, which is usually used for children and isn’t very easy. With this test, you give a substrate and have the patient breathe out radio-labelled carbon dioxide. Because it’s nuclear medicine, arranging the test can be extremely cumbersome.”
“You can also do a biopsy through endoscopy or surgery and then attempt to grow the organism from the tissue. As you can imagine, this method is very invasive. It requires many resources, including hospital time, pathology analysis and lab work.”
In addition to the blood and stool test, the breath test is also used to identify individuals who are believed to be infected with H. pylori.
Alexander said his greatest hope for detecting the disease is via stool samples. “It’s the most direct in detecting H. pylori cells in the body. We have high hopes for using genomics on these samples because we know that H. pylori bacteria can be found via a standard stool antigen test.”
While difficult to diagnose, treatments are available for those infected by H. pylori, mainly via administering a cocktail of antibiotics. Treatments usually involve a combination of antibiotics, proton pump inhibitors, and other medications to eradicate the infection and promote the healing of the affected tissues. However, the effectiveness of these approaches is unpredictable, mainly because knowledge about the nature of H. pylori as a bacterium is relatively limited.
“H. pylori is so difficult because it requires multiple medications, but often the bacteria are resistant. Sometimes patients fail treatment and being unable to determine resistance, doctors treat the patient with multiple courses of antibiotics or different antibiotics just hoping they will be effective,” said Reimer.
“Four to six antibiotics are mainly used to fight H. pylori. Most of the time, the treatment is successful, but for about 30% of patients, antibiotics won’t work, and then you have a problem.”
Alexander is also concerned with the current treatment regimen and the possible impacts of antibiotic resistance. “We have an incredibly unusual organism that, if left untreated, could lead to gastric cancer. Unless we eliminate the organism, it will become more resistant, which means the future treatment could be tough.”
The ability of H. pylori to colonize the stomach and persist for long periods is attributed to its remarkable adaptability and survival mechanisms. One of its distinguishing features is its ability to withstand the stomach’s acidic environment, which is inhospitable to most other microorganisms. H. pylori survives the acid attack by producing an enzyme called urease, which converts urea into ammonia which neutralizes stomach acidity and makes the stomach hospitable for survival.
“The genomics of H. pylori are fascinating. Researchers have discovered that you can trace the bacteria’s geographic origin based on the genome profile,” said Alexander. “So it appears these organisms are travelling with families or cultural groups.”
Understanding the epidemiology and transmission of H. pylori, especially within specific populations, has been a subject of great interest for researchers. The bacterium is believed to be primarily transmitted through oral-oral or fecal-oral routes, often occurring within families or communities with poor sanitation. Factors such as socioeconomic status, crowded living conditions, and hygiene practices can influence the prevalence of H. pylori in different populations.
“This is a gastrointestinal pathogen, so the current belief is it gets out of the stomach and is transmitted. How H. pylori is spread is still unknown because it’s an indolent infection. It’s not something that causes acute illness right away. That means telling a patient how they got H. pylori is almost impossible when you don’t know when or where they were infected,” said Alexander.
“Is it spread from person to person? Is it from food? Is it from the surrounding environment? Is it in the water supply? It could be some or even all those things, but the strains we look at seem to travel within family or community groups.”
H. pylori, said Alexander, appears to have high infection rates and more significant health impacts on indigenous and new immigrant populations in Canada. Alexander suspects access to health supports is one of the main factors for higher infections.
“I think there are two main reasons this pathogen has hit indigenous and new immigrant communities harder. One is barriers to accessing healthcare. The outcomes can be more negative if a diagnosis is made well after infection. The other is related to infection rates. The higher prevalence of infection within the community, the more likely you will see worse outcomes.”
Another significant objective of the H. pylori Genomics Project will be to understand the genomic structure of the bacterium to help physicians pinpoint the most effective antimicrobial treatments. Alexander indicated the project would focus its lab research using a metagenomics approach in analyzing biopsy and stool samples.
“Where this project will push boundaries is how DNA samples are prepared to maximize what we can sequence,” said Alexander. “If we can tweak our approach, we aim to find a better way of sequencing more of the H. pylori and less of the stuff we are not interested in.
“With biopsy samples, not much stuff lives in the stomach. H. pylori should be there, but not very many other organisms. So the trick here is to ensure we’re sequencing bacterial DNA, not human stomach DNA.
“Stool samples are more complicated because it’s a complex matrix filled with all sorts of stuff, making analysis pretty challenging.
“We’re looking at a couple of different approaches. One is the shotgun metagenomics approach, which means we just sequencing everything.
“The other is a sample preparation approach called bait capture. The goal is to capture pieces of H. pylori DNA relative to other stuff. For example, we may use a more traditional targeted PCR [Polymerase Chain Reaction – a way of amplifying small pieces of DNA] to identify only the most meaningful pieces of H. pylori DNA. Specifically, the ones that provide information about a strain’s antibiotic resistance.”
The H. pylori Genomics Project will also focus on developing “susceptibility profiles” for regions within Canada. In doing so, the project team hopes to create a more precise diagnostic model for front-line physicians and specialists of what strains of H. pylori are likely to exist in certain parts of Canada. Knowing the strain can help in prescribing more effective antibiotic treatments.
“We had samples in Manitoba that, through genomic sequencing, we found are different from samples taken from northern Alberta,” said Alexander. “We just don’t know if those differences are meaningful for pathogenicity. That work is ongoing.”
“We know that H. pylori antimicrobial resistance rates will be different in some areas of the country,” said Reimer. “By collecting and sharing data, Canadian doctors would have better information. So, a doctor in Edmonton could provide treatment for patients in northern Alberta by accessing the susceptibility profile of that region.
“We believe this project will greatly advance the goal of reducing the societal and economic impact of H. pylori on Canadians, as well as reducing antimicrobial resistance.”
The Helicobacter pylori Genomics Project is scheduled to conduct its research between the publication of this article and 2026. The $1.6M project is jointly funded by the National Microbiology Laboratory (NML), Genome Canada, The Cadham Provincial Laboratory, Alberta Precision Laboratory, McMaster University, Illumina Corp, and the Roy Romanow Provincial Laboratory. For more information about the project, please visit genomeprairie.ca
