Helicobacter pylori is one of the most prevalent causes of persistent bacterial infections in humans, affecting over half of the world's population.
H. pylori can cause stomach irritation (gastritis) as well as an increased risk of stomach cancer. Because the stomach’s protective lining is constantly exposed to stomach acid, it must regenerate every few weeks while preserving its shape and content despite the fast cellular turnover. A group of Molecular Medicine (MDC) experts has been able to decipher the changes that occur inside the stomach glands during an H. pylori infection.
The researchers found a unique mechanism that protects the stomach from malignant alterations by inhibiting cell division in healthy stomach tissue. Inflammation in the stomach, on the other hand, disables this function, allowing cells to grow uncontrollably.
The researchers’ findings, which have been published in Nature Communications, may herald a new treatment target in stomach cancer.
“Until now, researchers had assumed that a Helicobacter infection causes direct damage to the gastric gland cells in the stomach lining and that gastric pathology upon infection is simply the result of this process,” explains the study’s last author, Prof. Dr. Michael Sigal. “In fact, our team has now discovered that the infection disrupts complex interactions between different cell types and signals which are responsible for tissue stability.”
The team of researchers employed complicated animal models to detect alterations occurring inside the stomach glands, led by Prof. Sigal and collaborating with Max Planck Institute for Infection Biology. The researchers were able to detect and isolate specific stomach gland cells using cutting-edge imaging and single-cell sequencing technology, which they subsequently investigated in depth. They also designed special organ-like tissue microstructures known as organoids to reduce the requirement for animal models.
‘Bone morphogenetic proteins’ (BMPs) are among these chemicals, and they play a crucial role in tissue formation. The researchers were able to demonstrate that stromal cells surrounding the gland base continuously suppress the BMP signalling pathway, causing adjacent stem cells to proliferate. The signalling pathway was discovered to be activated by stromal cells near the gland surface, which suppressed cell proliferation. This creates a signalling gradient that controls stem cell turnover and differentiation while also ensuring the gland’s structural integrity. The release of pro-inflammatory chemicals such as interferon-gamma (IFN-) is triggered by Helicobacter infection. This inflammatory cytokine disrupts the BMP signalling axis, leading in reduced BMP activity and increased gland stem cell growth.
Hyperplasia, a precancerous lesion marked by tissue expansion, is the result of this.
“Our findings show that an infection-driven inflammatory response has far more pronounced effects than previously thought. In addition to their well-characterized antimicrobial effects, pro-inflammatory substances such as IFN-γ affect both cell proliferation and tissue stem cell behavior and therefore have a direct impact on tissue homeostasis. In the case of tissue damage, increased cell proliferation can be useful, as it promotes rapid healing. In the case of chronic inflammation associated with a Helicobacter infection, however, it could facilitate the development of precancerous lesions,” summarizes Prof. Sigal.
The mechanisms that govern interactions between the immune system and stem cells in the stomach may also be significant in other organs. As a result, they’re a viable new cancer prevention and regenerative medicine therapeutic target.