Helicobacter pylori

Helicobacter pylori is a Gram-negative rod-shaped bacterium. It infects the mucous membrane of the stomach in more than half of the world’s population and is therefore one of the most common bacterial infectious agents of all. The infection is usually acquired in childhood and persists for decades if not actively treated.

Infection with H. pylori always causes an inflammatory reaction of the stomach mucosa, which can be detected in a fine tissue examination of the stomach. However, it does not necessarily cause any symptoms; more than 80 % of those infected remain asymptomatic. However, secondary diseases can develop on the basis of H. pylori gastritis. The most important secondary diseases are

• Stomach ulcer
• Duodenal ulcer
• Stomach cancer (adenocarcinoma)
• Lymphoma of the stomach (MALT lymphoma)

Diagnostic evidence of H. pylori infection is usually obtained during a gastroscopy, where samples (biopsies) are taken and examined for H. pylori. It is also possible to detect an
H. pylori infection by a breath test or a stool test.

A vaccination against H. pylori is currently not available.

Therapy is carried out with a combination of antibiotics and acid secretion inhibitors. The aim of the therapy is the complete elimination of the pathogens from the patient’s body (eradication). Since the risk of infection among adults in Germany is low, the risk of acquiring an H. pylori infection again after successful eradication therapy is also very low (less than 1% per year).

Helicobacter pylori and cancer

An existing infection with H. pylori increases the risk of stomach cancer by a factor of 4-6. H. pylori has been officially classified as a carcinogen since 1994, and this classification was confirmed in 2009.

As with many other carcinogens, H. pylori infection only leads to cancer in a small proportion of those infected, and there are usually decades between infection and the onset of cancer. This makes it difficult to prove the effect of a therapy on the incidence of cancer. However, there are now several studies from countries with high H. pylori infection rates and high gastric cancer incidence that show that in such countries, consistent treatment of H. pylori infections can reduce gastric cancer mortality. Therefore, in many countries, treatment of every H. pylori infection is now recommended for cancer prophylaxis. In Germany, the current DGVS guideline recommends offering patients eradication therapy even in cases of asymptomatic H. pylori infection.

The group led by Prof. C. Josenhans joined the Max von Pettenkofer Institute in the fall 2017.

The gastrointestinal tract of humans and most vertebrate organisms is at the same time the largest body surface, colonization niche of a variety of different microbes, as well as the most important barrier and entry point of gastrointestinal and some systemic pathogens. Gastrointestinal pathogens, in particular bacteria, are adapted in a specific manner to the mucosal niche of the gut and stomach lining. They assemble complex secretion systems, which help them to be motile within the mucus, and establish contact and interactions with the host and local host cells. Likewise, they possess metabolic and other factors, which enable them to compete with the resident microbiota of the gut and surmount colonization resistance. In addition, they are able, with the help of specific factors and functions, to influence the composition of the resident microbiota and the inflammatory response of the local tissues, in order to govern their own temporal and spatial persistence within the niche.

Major scientific interest in the Josenhans lab is on the host innate immune response towards gastrointestinal pathogens and its modulation. In this context, the modulatory activity of bacterial complex secretion systems (type 3, type 4, type 6) on the host cell is investigated, including the biochemical and structural characterization of its protein components. The lab also addresses questions concerned with gene and protein regulation and modification in host and pathogen, also during the infectious process. A second focus is placed on host modulation by pathogens and the modulation of inflammatory diseases, also with respect to environmental factors, including the resident gastrointestinal microbiota. Main model systems to study chronic and acute gastrointestinal bacterial pathogens are the human pathogens Helicobacter pylori and Campylobacter jejuni as well as the chronic mouse gut pathogen Helicobacter hepaticus, which can serve as a model for chronic inflammatory diseases. We also place a major emphasis on the factors that activate and modulate the host innate immune system (human but also others), and, on the host side, the receptors and signal transduction pathways that are invoved in the host innate immune response.

Our group performs both basic and translational research aiming at better understanding, diagnosing, treating and preventing infections of the gastrointestinal tract. Our main focus is on the human gastric carcinogen, Helicobacter pylori, where we use a combination of experimental approaches and comparative genomics to understand the genetic variability of H. pylori and its role in adapting the pathogen to its human host. Other projects study the genome of the most important human diarrheal pathogen in Germany, Campylobacter jejuni, the mouse pathobiont, Helicobacter hepaticus and its role in inflammatory bowel disease, and the role of the intestinal and gastric microbiota in health and disease.