Risk Marker for Stomach Cancer Uses Acid Sensors to Control Colonization

New research from a team of scientists from Stanford University and the University of Oregon could hold the key to understanding how to use the presence of a certain bacteria in the gut of more than half of all humans could be putting them at risk for stomach cancer.

The researchers examined Heliobacter pylori, a spiral-shaped bacterium that lives in the mucosal layer of the stomach. In most patients, H. pylori does not cause any negative symptoms in the infected person and, in fact, the bacterium “co-evolved with humans since the origin of the human species,” the team noted in the study. Although the bacterium can only inhabit a very small area of the stomach—within 25 microns of the surface of the stomach lining—and is actually averse to the acid secretions of the stomach, it is infectious and, furthermore, is probably responsible for more than 90% of ulcers in the small intestine and possibly up to 80% of other gastric ulcers.

Because the presence of the bacterium is so often associated with ulcers and atrophic gastritis, both of which are associated with an increased incidence of gastric cancers, many researchers speculate that the bacterium could actually serve as a risk marker or even a cofactor for stomach cancer. The Stanford team’s work analyzing what drives the bacteria into “hiding” from acidic areas of the stomach could have major implications for treating H. pylori infections and proactively monitoring patient health for future health threats.

Using a mouse model, the researchers found that H. pylori use special sensors, called chemoreceptors, to constantly sense acid and flee the acidic area, usually burrowing into the protective mucus layer on the interior of the stomach. When the bacteria infiltrate stomach glands and the stomach lining, the situation is prime for infection and the formation of ulcers. In humans, once the ulcers form, patients and practitioners often treat the symptoms of the ulcers—including stomach pain, nausea, vomiting, bleeding, and loss of appetite—with proton pump inhibitors (PPIs) that reduce stomach acid production and relieve symptoms. PPIs do not eliminate the problem, though, since H. pylori actually thrive in lower levels of stomach acidity, allowing the infection to spread. This was evidenced in the study when the researchers found that the bacterium was able to colonize much farther into study animals’ gastric glands when they were treated with omeprazole, a common medication used to reduce stomach acid, alleviate symptoms of dyspepsia, and prevent gastrointestinal bleeding.

H. pylori navigate the stomach using two chemoreceptors, TIpA and TIpD, both of which allow the bacterium to respond to very small changes in acid levels. “H. pylori mutants lacking both TIpA and TIpD are unable to sense acid and are severely impaired in their survival,” noted study team leader Manual Amieva, MD, PhD, associate professor of Pediatric Infectious Diseases and Microbiology and Immunology at Stanford University in a report. He added that these receptors also control how the bacteria interacts with the stomach lining, noting that not only do the receptors control a fleeing impulse when the bacteria detect high acidity, but that they also may cause H. pylori to “swarm” toward particularly basic areas of the stomach.

In light of these results, research also published in early 2017 in the New England Journal of Medicine could shed light on how patients with H. pylori infectious should be diagnosed and treated. The NEJM study indicates that H. pylori infections are associated with an increased risk of stomach cancer and could even be a cofactor in patient development of stomach cancer.

“It is clear that infection with H. pylori alone cannot explain the pathogenesis of gastric carcinoma,” the researchers wrote, adding that infections beginning in childhood might be particularly likely to increase the risk of cancer in adult patients.

The Centers for Disease Control and Prevention (CDC) recommends that any patients with a documented history of ulcers should be tested for H. pylori when presenting for treatment. It is possible that these patients should also be monitored more closely after treatment to prevent recurrent infections and the associated increased cancer risk.

CDC researchers also speculate that H. pylori can be passed from one person to another either from eating food containing fecal matter containing the bacterium, or mouth-to-mouth; the actual method of infection is unknown. Environmental reservoirs of the bacterium, such as contaminated water sources, have been traced as sources for infections in the past.

H. pylori can be eradicated using antibiotics and, in some cases, that treatment is supplemented with an acid suppressor to alleviate painful ulcer symptoms and expedite healing. In cases where acid in the stomach is suppressed, H. pylori might swarm to a more basic area, based on the Stanford team’s conclusions, thereby increasing risk of a subsequent infection if any survive an antibiotic regimen. To this end, Dr. Amieva and his team noted that in humans, cancer and associated pathology might be associated with the location and distribution of the H. pylori infection, stating, “Our study and others support the clinical recommendation that patients considered for long-term PPI treatment first be tested and treated for H. pylori infection.”