Interaction of Helicobacter pylori (Hp) and nonsteroidal anti-inflammatory drugs (NSAID) on gastric mucosa and risk of ulcerations.

Hp and NSAID are the most common pathogens in the stomach, but their interaction on gastro-duodenal mucosa has been little studied. Hp infection in humans does not interfere with NSAID-induced gastric ulcer healing by omeprazole, therefore, there is no rationale to eradicate the germ. Hp infection induces COX-2 expression resulting in excessive biosynthesis of gastroprotective prostaglandin (PG), which should in turn counteract NSAID-induced gastropathy and contribute to healing of existing ulcers. Some investigators claim that Hp infection acts synergistically with NSAID on ulcerogenesis and propose that Hp should be eradicated, particularly at the onset of long-term NSAID therapy. Our studies in about 6500 dyspeptic patients undergoing upper endoscopy and 13C-urea breath test revealed that about 70% of these patients are Hp positive and 31% of these develop gastro-duodenal ulcers. Of these ulcers, 66% were Hp positive and NSAID negative, 3%--NSAID positive and Hp negative, 8% were both Hp positive and NSAID positive, while 23% ulcers were Hp and NSAID negative. An evidence was obtained for negative interaction between Hp infection and NSAID on risk of gastro-duodenal ulcers suggesting that Hp may attenuate the peptic ulcerogenesis. Our results support the concept 1) the interaction between Hp infection and NSAID on gastro-duodenal ulcerations is antagonistic, 2) the Hp and NSAID are independent risk factors for peptic ulcerations in humans, 3) there is no need for the Hp eradication in NSAID-treated patients, and 4) the rate of ulcer complications (hemorrhage and perforation) remains constant despite the decrease in Hp and ulcer prevalence.

Impact of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on gastric ulcerogenesis in experimental animals and in humans.

Helicobacter pylori (H. pylori) and nonsteroidal anti-inflammatory drugs (NSAID) are the most common pathogens in the gastroduodenal mucosa in animals and humans, but their relationship in ulcerogenesis has been little studied. According to some authors, H. pylori infection in humans does not act synergistically with NSAID on ulcer healing, therefore, there is no need to eradicate the germ. This notion is supported by the finding that the eradication of H. pylori does not affect NSAID-induced gastropathy treated with omeprazole and that H. pylori infection induces a strong cyclooxygenase-2 expression resulting in excessive biosynthesis of gastroprotective prostaglandins, which should in turn counteract NSAID-induced gastropathy and heal the existing ulcer. Other investigators claim that H. pylori infection acts synergistically with NSAID on ulcer development, therefore, H. pylori should be eradicated, particularly at the start of long-term NSAID therapy. Maastricht 2-2000 consensus also recommends eradication prior to NSAID treatment, but this eradication does not appear to accelerate ulcer healing or to prevent the recurrent ulcers in NSAID users. Our studies in almost 6,000 dyspeptic patients undergoing upper endoscopy and [(13)C]-urea breath test (UBT) revealed that about 70% of these patients are H. pylori (+) and about 30.6% of these develop gastroduodenal ulcers. Of these ulcers, over 70% were H. pylori (+) positive, 12% NSAID (+), 8% were both H. pylori (+) and NSAID (+), while 22% ulcers were H. pylori (-) and NSAID (-) or "idiopathic" ulcers. Basically, our results support Hawkey's concept and this also agrees with our findings in the rat model showing that: (1) there is no synergistic interaction between H. pylori infection and NSAID on gastric ulcer development, (2) H. pylori and NSAID are independent risk factors for peptic ulceration, and (3) NSAID therapy in H. pylori positive patients attenuates the ulcer development possibly due to direct inhibitory action of these drugs on H. pylori.

Oral cavity as a potential source of gastric reinfection by Helicobacter pylori.

Helicobacter pylori (Hp) is a common pathogen colonizing the a gastric mucosa, but some reports indicated that it may also be found in the oral cavity, which could serve as a reservoir of the bacteria and a source of gastric reinfection. Accordingly, we aimed to study whether the oral cavity, particularly gingival pockets, are colonized by Hp and whether it could be the source of gastric reinfection. We studied 329 patients with dyspeptic symptoms (257 with chronic gastritis, 15 with gastric ulcer, and 57 with duodenal ulcer). The [13C]urea breath test (UBT), gastroscopy, and Hp culture from gastric biopsies were carried out, and material was collected from the oral cavity (gingival pocket) for bacteriological culture and genomic DNA studies. The serum was obtained for anti-Hp IgG and anti-CagA assays and saliva for anti-Hp IgA determination using the ELISA technique. Bacteria in material from gingival pockets and biopsies from the corpus and antrum of stomach of 30 DU patients before and after Hp eradication were also examined by PCR technique, using primers specific for 16S rRNA. All Hp-positive patients (276) were subjected to one week of triple therapy (omeprazole 2 x 20 mg twice a day, clarithromycin 2 x 500 mg twice a day, and metronidazole 2 x 500 mg twice a day). The measurements described above were then repeated at four weeks and six months. Bacteriological culture showed the presence of Hp in the material from oral cavity in about 50% of patients, whereas UBT, used as a gold standard, revealed gastric Hp infection in about 84% of these patients. The eradication was successful in the majority of patients (87%), but about 13% of them were still Hp positive after four weeks and about 21% after six months. Four weeks after Hp therapy, Hp was found in culture from oral samples in 23% (P < 0.05 vs initial) and after six months in 35.1%. The IgA levels recorded in saliva were in a close agreement with UBT results. Hp DNA assessed by PCR in 30 DUs before eradication of Hp was detected in 95% of antral mucosa, 90% in corpus mucosa, and in 35% of gingival pocket material, and after eradication therapy Hp DNA values fell to 25%, 20%, and 10%, respectively. In conclusion, Hp is commonly detected in the oral cavity of patients with dyspeptic symptoms, but the gastric reinfection does not appear to occur in the patients despite oral Hp colonization.