HMN 2026: How H. pylori uses extracellular vesicles to drive stomach cancer

Scientists at the Hudson Institute of Medical Research have discovered how Helicobacter pylori, the bacterium responsible for most stomach cancers and peptic ulcers, delivers a key disease-causing protein into human cells. This breakthrough provides new insight into how H. pylori modulates chronic inflammation and promotes cancer, potentially opening new diagnostic and therapeutic pathways.

Led by Jack Emery and Professor Richard Ferrero, the study shows for the first time that a poorly understood H. pylori virulence factor, known as Tip? (tumor necrosis factor-?-inducing protein), is not simply secreted into the stomach environment. Instead, it is packaged inside tiny nanoparticles called extracellular vesicles (EVs), microscopic “delivery pods” that transport bacterial molecules into human cells.

This discovery, published in the Journal of Extracellular Vesicles, positions the Hudson Institute as a global leader in H. pylori biology and provides crucial new insights into how the bacterium contributes to stomach cancer, which remains one of the world’s deadliest cancers.

A global infection with deadly consequences

Helicobacter pylori infects 43.9% of the global population (4.4 billion people worldwide). In many regions, including Africa, Eastern Europe and Southeast Asia, prevalence exceeds 50%. While many people never experience symptoms, H. pylori is responsible for:

• 90% of non-cardia stomach cancers
• 92% of MALT lymphomas
• a major proportion of peptic ulcers

Stomach cancer has a five-year survival rate of just 40%, largely because it is often diagnosed late.

“Understanding how H. pylori manipulates stomach cells is essential if we want to understand and prevent cancer,” said Jack Emery, first author of the study. “Antibiotics can clear the infection, but once cancer develops, treatment options are limited. We need new tools, and that starts with understanding the biology.”

A protein with a long-standing mystery

Tip? has been known to scientists for years. It is found in every H. pylori strain that infects the stomach and was linked to inflammation and cancer development. But previous studies produced conflicting results about what Tip? actually does.

Some research suggested Tip? triggers strong inflammation, particularly by increasing TNF—a key inflammatory molecule. Other studies hinted that Tip? might behave differently depending on the strain. The Hudson team’s findings resolve these contradictions by showing that Tip? behaves differently when delivered by extracellular vesicles.

“This was the missing piece,” Emery said. “Tip?’s behavior only makes sense once you understand how it is transported into cells.”

The team also found that the amount of Tip? secreted in EVs varies among different H. pylori strains. It remains an open question whether the amount of Tip? that is secreted correlates with cancer risk.

Using biochemical analysis, imaging and cell-based experiments, the researchers uncovered several major findings:

• Tip? is packaged inside H. pylori extracellular vesicles: This is the first biochemical evidence that an H. pylori virulence factor is packaged within, and not outside, EVs.
• EVs are the main mechanism of Tip? secretion: Contrary to previous assumptions, Tip? is not freely released; it is primarily released from the bacteria in EVs.
• EVs deliver Tip? directly into the nucleus of human stomach cells: Once inside the nucleus, Tip? binds to host DNA.
• EV-associated Tip? suppresses inflammation: This overturns earlier studies that claimed Tip? increases inflammation.

“We found that when Tip? is delivered via EVs, it can actually temper the inflammatory response,” Emery said. “It reduces production of TNF and IL-8, which may help H. pylori persist in the stomach for decades.”

This ability to dampen inflammation may create the chronic, low-grade inflammatory environment that eventually leads to stomach cancer.

Ferrero said the discovery provides a new perspective on how H. pylori interacts with host cells to cause disease and may be relevant to other bacterial infections. “It is the first time a bacterial virulence factor has been shown to be primarily secreted via extracellular vesicles. It also helps explain how H. pylori can manipulate the immune system without invading host cells.”

Why this discovery matters for patients

Because stomach cancer is often diagnosed late, prevention and early detection are critical. The team’s findings open several promising avenues:

• New biomarkers for early detection: Tip?-containing EVs may be detectable in blood, saliva or gastric fluid, offering a potential early warning sign of infection or cancer risk.
• New vaccine targets: Understanding how Tip? is packaged and delivered may help researchers design vaccines that block this process.
• New therapeutic strategies: If Tip? helps H. pylori evade the immune system, targeting EV-mediated delivery could weaken the bacterium’s ability to persist.

“Ultimately, one of our goals is to develop better tools to identify those individuals who are most at risk and prevent cancer before it develops,” Emery said.

A global collaboration led from Melbourne

The research was led by Ferrero’s group at Hudson Institute and involved collaborators from UNSW Sydney and international partners in Thailand, Brazil, the United States and France, reflecting the global importance of H. pylori research.

His group is internationally recognized for its pioneering work on H. pylori pathogenesis.

“This discovery reinforces Hudson’s position as a leader in H. pylori research,” Ferrero said. “Our team has been working on this bacterium for many years, and this study represents a major step forward in understanding its biology and how it causes disease.”

What comes next?

The team is now investigating:

• how Tip? interacts with human DNA
• whether Tip?-containing EVs can be detected in patient samples
• how EV-mediated delivery influences long-term cancer risk
• whether blocking EV formation could weaken H. pylori infection

“We’ve uncovered a completely new mechanism of bacterial communication,” Emery said. “Now we want to understand how we can use that knowledge to help patients.”

A major step toward preventing stomach cancer

With stomach cancer ranking fifth globally for both incidence and mortality, the need for new prevention strategies is urgent.

By revealing how H. pylori uses extracellular vesicles to deliver a key virulence factor into human cells, Hudson researchers have opened the door to a new mechanism by which the bacterium causes disease. “This is the kind of fundamental discovery that is essential if we want to develop new diagnostics or treatments and make stomach cancer far more preventable,” Ferrero said.

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