Helicobacter pylori colonization critically depends on postprandial gastric conditions.

The risk of Helicobacter pylori infection is highest in childhood, but the colonization process of the stomach mucosa is poorly understood. We used anesthetized Mongolian gerbils to study the initial stages of H. pylori colonization. Prandial and postprandial gastric conditions characteristic of humans of different ages were simulated. The fraction of bacteria that reached the deep mucus layer varied strongly with the modelled postprandial conditions. Colonization success was weak with fast gastric reacidification typical of adults. The efficiency of deep mucus entry was also low with a slow pH decrease as seen in pH profiles simulating the situation in babies. Initial colonization was most efficient under conditions simulating the postprandial reacidification and pepsin activation profiles in young children. In conclusion, initial H. pylori colonization depends on age-related gastric physiology, providing evidence from an in vivo infection model that suggests an explanation why the bacterium is predominantly acquired in early childhood.

Specific therapeutic schemes of omeprazole affect the orientation of Helicobacter pylori.

Until now, it has been unclear how proton pump inhibitors (PPIs) support Helicobacter pylori therapy. We tested whether the PPI omeprazole acts on the spatial orientation of H. pylori in the gastric mucus of infected Mongolian gerbils. Following repetitive PPI administration once daily but not following single doses or administration every 8 h, the bacterial spatial distribution changed, indicating a loss of orientation. Therefore, the therapeutic scheme of PPI administration may affect efficiency of treatment.

Tracing of gastric reflux into the middle ear in a mongolian gerbil model.

OBJECTIVES: The purpose of this study was to trace induced gastric reflux and to examine whether it reaches the middle ear in a Mongolian gerbil model. BACKGROUND: Otitis media with effusion is the most frequent middle ear disease in childhood. Gastroesophageal reflux is suspected to be a possible factor in its pathogenesis. METHODS: Seventeen Mongolian gerbils were assigned to three groups: the control (phosphate-buffered saline application to the lower esophageal sphincter) and two experimental groups (Aquo-Trinitrosan [Merck, Darmstadt, Germany] application to the lower esophageal sphincter, low gastric pressure and Aquo-Trinitrosan application, higher gastric pressure). We injected Chinese ink into the stomach to trace the path of a potential gastroesophageal reflux in all three groups. The traces of ink were investigated by ear and larynx endoscopy and histology. RESULTS: There were no signs of gastroesophageal reflux based on the data obtained from the control group. In animals with traceable laryngeal reflux, the ink was also shown to advance through the eustachian tube and reach the middle ear. In addition, we found that when reflux reaches the middle ear on one side, it also reaches the contralateral middle ear in most cases. CONCLUSION: Gastroesophageal reflux induced by relaxation of the lower esophageal sphincter was shown to reach the middle ear in our Mongolian gerbil model. These results support recent hypotheses linking gastroesophageal reflux to the development of otitis media with effusion.

Gastric antibacterial efficiency is different for pepsin A and C.

The gastric lumen represents a bactericidal barrier, whose major components are an acidic pH and a family of isoenzymes of the gastric aspartate protease, pepsin. To evaluate whether specific pepsins are specialized in antibacterial protection, we tested their effects on the gastric pathogen Helicobacter pylori. In a recent study we found pepsin to affect the motility of the bacteria, one of its most important virulence factors. We were able to show that the antibacterial effect of pepsin occurs in two phases: rapid loss of motility and subsequent destruction. In the present study we used the rapid pepsin-induced bacterial immobilization as a marker of antibacterial efficiency. The proteolytic activity of different pepsins was normalized to values between 2 and 200 U/ml in the hemoglobin degradation test of Anson, performed at pH 2 and 5. We found that pepsin C completely inactivates H. pylori at proteolytic activities of 2 (pH 5) and 20 (pH 2) U/ml. In contrast, the activities of pepsin A and chymosin required to affect Helicobacter motility were ten times higher.

Rapid loss of motility of Helicobacter pylori in the gastric lumen in vivo.

The human pathogen Helicobacter pylori has infected more than half of the world's population. Nevertheless, the first step of infection, the acute colonization of the gastric mucus, is poorly understood. For successful colonization, H. pylori must retain active motility in the gastric lumen until it reaches the safety of the mucus layer. To identify the factors determining the acute colonization, we inserted bacteria into the stomach of anesthetized Mongolian gerbils. We adjusted the gastric juice to defined pH values of between 2.0 and 6.0 by using an autotitrator. Despite the fact that Helicobacter spp. are known to survive low pH values for a certain time in vitro, the length of time that H. pylori persisted under the assay conditions within the gastric juice in vivo was remarkably shorter. In the anesthetized animal we found H. pylori to be irreversibly immotile in less than 1 min at lumen pH values of 2 and 3. At pH 4 motility was lost after 2 min. However, the period of motility increased to more than 15 min at pH 6. Blocking pepsins in the gastric lumen in vivo by using pepstatin significantly increased the period of motility. It was possible to simulate the rapid in vivo immotilization in vitro by adding pepsins. We conclude that pepsin limits the persistence of H. pylori in the gastric chymus to only a few minutes by rapidly inhibiting active motility. It is therefore likely that this short period of resistance in the gastric lumen is one of the most critical phases of Helicobacter infection.

The spatial orientation of Helicobacter pylori in the gastric mucus.

The highly motile human pathogen Helicobacter pylori lives deep in the gastric mucus layer. To identify which chemical gradient guides the bacteria within the mucus layer, combinations of luminal perfusion, dialysis, and ventilation were used to modify or invert transmucus gradients in anaesthetized Helicobacter-infected mice and Mongolian gerbils. Neither changes in lumen or arterial pH nor inversion of bicarbonate/CO2 or urea/ammonium gradients disturbed Helicobacter orientation. However, elimination of the mucus pH gradient by simultaneous reduction of arterial pH and bicarbonate concentration perturbed orientation, causing the bacteria to spread over the entire mucus layer. H. pylori thus uses the gastric mucus pH gradient for chemotactic orientation.