Infection with the Helicobacter pylori germ leads to chronic gastric mucosal inflammation in all those affected, and gastric cancer to some of those infected. 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 worked in cooperation with the University Clinic for Gastroenterology, Hepatology and Infectiology at Otto von Guericke University Magdeburg (OVGU) carried out a joint study as part of a newly launched clinical leave program to promote young scientists.
Samples of Helicobacter-infected patients from the oral cavity to the small intestine were obtained endoscopically and examined for the first time using high-throughput sequencing based on the RNA profiles in comparison with non-infected patients. The result: Everyone shows their own, very individual microbiome from the oral cavity to the small intestine. If there is an infection with H. pylori, the pathogen very quickly dominates the microbial colonization of the gastric mucosa and, due to its special properties, displaces other useful neighbors. In particular, Helicobacter also influences the microbial composition of both the oral cavity and the small intestine. In the future, this knowledge may lead to new approaches for the prevention and therapy of this most common bacterial infection in humans. The scientists recently published their results in the journal Gut.
Around 50 percent of all people worldwide are infected with Helicobacter pylori. About 80 percent of all infected people are symptom-free. However, the infection can also have fatal consequences for patients, ranging from stomach cancer. About 90 percent of gastric cancer can be attributed to Helicobacter. It was only in 1989 that the bacterium was recognized as the cause of stomach ulcers and stomach cancer and this connection was awarded the Nobel Prize in Medicine in 2005.
Helicobacter pylori can attach to the epithelial cells of the gastric mucosa using special adhesive structures. To protect themselves from stomach acid, the germs can use the urease enzyme to raise the pH in their immediate vicinity. "Since the germs also produce substances that damage the mucous membrane, colonization leads to permanent inflammation of the gastric mucosa," explains Prof. Peter Malfertheiner, director of the University Clinic for Gastroenterology, Hepatology and Infectiology of the Medical Faculty of the Otto von Guericke University Magdeburg. "The result is an increased production of gastric acid, which can lead to gastric or duodenal ulcers." The diagnosis of Helicobacter infection is usually made by gastroscopy. Tissue samples are taken from different sections of the stomach.
"How the bacteria get into the stomach and what influence it has on the microbial community in the gastrointestinal tract has not yet been investigated in detail," says HZI scientist Prof. Dietmar Pieper, head of the "Microbial Interactions and Processes" working group. “The human stomach with its highly acidic environment is by no means a sterile place. We know from previous studies that not only the resistant bacterium H. pylori is able to colonize the intestinal mucosa. Other types of bacteria have also been isolated from gastric juice. ”Today it is known that the upper intestinal tract is home to a complex bacterial community. However, there is still very little knowledge about the microbial biodiversity of people who are infected with Helicobacter compared to healthy people. "This could give us information about whether the carcinogenic role of Helicobacter is alone or because of its disruptive influence on the so-called commensals, the harmless and useful neighbors in the stomach," says Pieper.
The aim of the joint study by the HZI researchers with the OVGU Magdeburg was therefore to carry out a continuous inventory of the microbiome of individual subjects from the oral cavity to the small intestine. "We were particularly interested in the microorganisms that get saliva from the oral cavity into the intestinal tract and whether they are able to colonize the gastric mucosa," says Pieper.
For the study, the microbiome of the upper digestive tract was examined in 24 patients, eight of whom had a detectable Helicobacter pylori infection. A total of over 120 patient samples were taken from the oral cavity, stomach and duodenum. Using the latest 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 each person has a very individual microbiome profile that runs consistently through the regions of the upper gastrointestinal tract," says Dietmar Pieper. A total of over 600 so-called phylotypes were detected in the samples. The microorganism community mainly consisted of Firmicutes, Bacteriodetes, Proteobacteria, Actinobacteria and Fusobacteria. “If Helicobacter pylori was present, it quickly dominated the entire colonization in the gastric mucosa. In addition, an infection with H. pylori also affects the microorganism community of the duodenum and oral cavity, ”says Pieper.
In further studies, the researchers will now examine the extent to which bacterial colonization in the oral cavity plays an important role in sensitivity to Helicobacter infections. The change in the bacterial microbiome in the duodenum due to an H. pylori infection in the stomach could also have a significant impact on the development of intestinal diseases.
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.doi: 10.1136 / gutjnl-2016-312904