A Marauder in the Microbiome
Miller School researchers are unlocking the mysteries of a carcinogenic bacterium
By Jen A. Miller
Illustration by Bill Mayer
acteria are swimming in our guts. That’s not necessarily a bad thing. Probiotics, for example, help us digest food, make vitamins, and destroy rogue, possibly cancer-causing mutated cells before they spin out of control. But bad actors can also sneak in and wreak havoc. That’s especially true with Helicobacter pylori (H. pylori), a bacterium that has infected about half the world’s population.
The clearest connection between H. pylori and bad health outcomes is with gastric cancer. H. pylori is typically passed from person to person as they share food and drinks, and it goes “right to the stomach and attaches itself to stomach cells,” said Wael El-Rifai, M.D., Ph.D., associate director of Basic Science and co-leader of the Tumor Biology Program at Sylvester Comprehensive Cancer Center. After binding to those cells, it injects CagA, an oncogenic bacterial protein, into them and reprograms cells.
An H. pylori infection “does not clear out by itself, and gradually causes chronic inflammation, which is a high risk factor for cancer,” he continued. This is a slow process, though — perhaps 40 or 50 years, as cells accumulate risk for mutations and damage to their DNA. Most people don’t know it’s there, and the infection may not present any outright symptoms, aside from occasional gastrointestinal distress. Because of a lack of symptoms in many patients, those gastric cancer cases are typically only discovered at stage III or IV, when the five-year survival rate is less than 25%.
“These infections can create all sorts of problems, often silently, until it’s too late,” Dr. El-Rifai said. “It’s important to understand the current state of H. pylori, the risks, and possible treatments.”
Above-average Rates of Mortality
Most infections are concentrated in Southeast Asian, Middle Eastern, and Latin American countries, homes to many of the immigrants who arrive in South Florida. As a result, residents of South Florida have above-average rates of mortality from gastric cancer. H. pylori rates are also high among veterans who served abroad, which is why the U.S. Department of Veterans Affairs is one of the funders for Dr. El-Rifai’s H. pylori research.
In January, the Miller School’s Wolfson Department of Community Service program, a student-run organization focused on increasing health care access equity, started conducting H. pylori screenings at health events around South Florida. Participants took a breath test and, if positive, were given antibiotics on the spot. They were also then connected to follow-up medical care.
That’s one way to tackle the problem, said Shria Kumar, M.D., a gastroenterologist and researcher at Sylvester. The other is to know which strains of H. pylori are more likely to incite gastric cancer. Dr. Kumar and colleagues are studying samples from endoscopies to do so.
Tipping the microbiome balance can have cascading effects on a person’s physical and mental health.
“We’re trying to put the pieces together to see what makes it more likely for this person with this strain to have it tip over into cancer,” she said.
That’s because H. pylori is tied to more than just gastric cancer. Tatjana Rundek, M.D., Ph.D., professor of neurology and scientific director at the Evelyn F. McKnight Brain Institute, is one of the researchers in the Northern Manhattan Study, a collaboration between the Miller School’s Department of Neurology and the Neurological Institute at Columbia University. The longitudinal study, which began in 1990, tracks cardiovascular disease and stroke risk factors in the diverse community of Northern Manhattan in New York City.
Connections to Other Infections
They have looked at the connection between H. pylori and other infections like herpes and chlamydia, and heart-related health problems like large artery stenosis, stroke risk, and carotid plaque thickness. They found that the higher the infectious burden, the higher the risk for developing heart disease and/or suffering a stroke. Dr. Rundek believes this is because inflammation spurs the creation of fibrinogen, a protein involved with blood clotting. While some fibrinogen is necessary to stop bleeding and repair wounds, too much of it is linked to thrombosis, vascular injury, and some kinds of cancer.
“Each of these kinds of infections may contribute to a little bit of exposure over the course of your life,” she said.
The link between heart disease and H. pylori isn’t as clear as with gastric cancer, she added, but is worth exploring further, as is determining if one of the infections included as part of the study is more likely to lead to a heart condition.
Right now, Dr. Rundek said, this kind of research is more focused on the cardiovascular effects of HIV, as those with HIV are at higher risk of heart failure, and COVID-19, particularly in patients suffering from long COVID, which can cause myocarditis, stress cardiomyopathy, heart attack, blood clots, and stroke.
Links to Mental Health
Miller School researchers are even exploring the possible links between H. pylori and mental health, said Eleonore Beurel, Ph.D., professor of psychiatry and behavioral sciences, and professor of biochemistry and molecular biology.
H. pylori is linked to a higher prevalence of T helper 17 (Th17) cells, which increase inflammation and help protect against infection. While Th17 cells can be useful, too many can lead to constant inflammation, so that instead of helping fight off an infection, they damage vital organs, including the brain. In mice, for example, high levels of Th17 cells are associated with depression, Dr. Beurel said.
While H. pylori is not the only bacterium to trigger a Th17 response — Dr. Beurel’s work has focused on the segmented filamentous bacteria — the tie between the two shows how tipping the microbiome balance can have cascading effects on a person’s physical and mental health.
“When you’re young, you get sick and get healthy, but when you get exposed long term, that inflammatory stress accumulates,” she said. “There’s so much we don’t know about bacteria and how they can affect us. We’re trying to unravel how these trillions of bacteria have an impact on everyday health.”