New study Helicobacter pylori infections affect our small intestinal flora

Infection with the germ Helicobacter pylori leads to chronic gastritis in all affected persons, in some of the infected to gastric cancer. In order to better understand the interaction of Helicobacter with the naturally occurring microorganism community in the upper digestive tract, scientists from the Helmholtz Center for Infection Research (HZI) in Braunschweig collaborated with the University Hospital for Gastroenterology, Hepatology and Infectious Diseases of the Otto von Guericke University Magdeburg (OVGU) carried out a joint study within the framework of a newly launched clinical leave program for the promotion of young scientists.

Here, samples of Helicobacter-infected patients from the oral cavity to the small intestine were obtained endoscopically and examined for the first time by means of high-throughput sequencing based on the RNA profiles in comparison with non-infected patients. The result: Each person shows his own, very individual microbiome throughout, from the oral cavity to the small intestine. If H. pylori infection is present, the pathogen very quickly dominates the microbial colonization of the gastric mucosa and displaces other useful neighbors due to its special properties. In particular, however, Helicobacter also influences the microbial composition of both the oral cavity and the small intestine. In the future, these findings may lead to new approaches for the prevention and treatment of this most common bacterial infection in humans. The scientists recently published their findings in the journal Gut.

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Worldwide, about 50 percent of all people are infected with Helicobacter pylori. About 80 percent of all infected people are asymptomatic. However, the infection can also have fatal consequences for patients, ranging to stomach cancer. About 90 percent of gastric cancers are due to Helicobacter. It was only in 1989 that the bacterium was recognized as the cause of gastric ulcers and gastric cancer, and in 2005 this award was awarded the Nobel Prize for Medicine.

Helicobacter pylori can attach to the epithelial cells of the gastric mucosa using special adhesive structures. To protect against stomach acid, the germs can use the enzyme urease to raise the pH in their immediate environment. "Since the germs also produce mucosal damaging substances, the colonization leads to a permanent inflammation of the gastric mucosa," explains Prof. Peter Malfertheiner, Director of the Department of Gastroenterology, Hepatology and Infectious Diseases of the Medical Faculty of Otto von Guericke University Magdeburg. "The result is an increased production of stomach acid, which can lead to gastric or duodenal ulcers." The diagnosis of Helicobacter infection is usually made by a gastroscopy. Tissue samples are taken from different sections of the stomach.

"How the bacteria gets into the stomach and what effect it has on the microbial life community in the gastrointestinal tract, has not yet been researched in detail," says HZI scientist Prof. Dietmar Pieper, head of the working group "Microbial interactions and processes". "The human stomach with its highly acidic environment is by no means a sterile place. From previous studies we know that not only the resistant bacterium H. pylori is able to colonize the intestinal mucosa. Other bacterial genera have already been isolated from the gastric juice. "Today it is known that the upper intestinal tract harbors a complex bacterial community. However, there are still very few findings on the microbial biodiversity of people who are infected with Helicobacter, compared to healthy people. "This could give us insight into whether the carcinogenic role of Helicobacter alone or through its disruptive effect on the so-called commensals, the harmless and useful neighbors in the stomach, arises," says Pieper.
The aim of the joint study of the HZI researchers with the OVGU Magdeburg was therefore to carry out a thorough inventory of the microbiome of individual subjects from the oral cavity to the small intestine. "We were particularly interested in the microorganisms that enter saliva from the oral cavity and whether they are able to colonize the gastric mucosa," says Pieper.

The study examined the microbiome of the upper digestive tract in 24 patients, eight of whom had a detectable Helicobacter pylori infection. More than 120 patient samples were taken from the oral cavity, stomach and duodenum. Using state-of-the-art sequencing methods and extensive bioinformatic analyzes based on the RNA profiles, the researchers were able to determine in great detail which microorganisms were metabolically active at the individual stations.

"In our investigations, we were able to demonstrate that every human being has a very individual microbiome profile, which is consistently drawn through the regions of the upper gastrointestinal tract," says Dietmar Pieper. In total, more than 600 so-called phylotypes were detected in the samples. The microbial community was composed mainly of Firmicutes, Bacteriodetes, Proteobacteria, Actinobacteria and Fusobacteria. "When Helicobacter pylori was present, it quickly dominated all of the gastric mucosal colonization. In addition, infection with H. pylori also affects the microorganism community of the duodenum and the oral cavity, "says Pieper.

In further studies, the researchers will now examine the extent to which the bacterial colonization in the oral cavity plays an essential role in the sensitivity to Helicobacter infections. The change in the bacterial microbiome in the duodenum due to H. pylori infection in the stomach could also have a significant influence on the development of intestinal diseases.

Original Publication:
The active bacterial assemblages of the upper GI tract in individuals with and without Helicobacter infection. Christian Schulz, Kerstin Schütte, Nadine Koch, Ramiro Vilchez-Vargas, Melissa L Wos-Oxley, Andrew P A Oxley, Marius Vital, Peter Malfertheiner, Dietmar H Pieper doo: 10.1136 / gutjnl-2016-312904