Effects of cagA+ and cagA- strains of Helicobacter pylori on the human gastric mucus layer thickness.

BACKGROUND: Infection with cytotoxin-associated gene A (cagA) Helicobacter pylori is associated with severe gastric diseases, with contradictory views being expressed concerning the effect of H. pylori on the gastric mucus thickness. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus thickness. METHODS: Ninety-nine patients without peptic ulcers who were not on medication were randomly recruited from consecutive endoscopy clinics: six biopsies (five antral, one body) were obtained from each patient. Cryostat sections (18 microm) were cut and stained using the modified periodic acid-Schiff/Alcian blue technique. Mucus thickness was measured using computer-assisted light microscopy. The H. pylori status was assessed by histology, Campylobacter-like organism (CLO)test and culture, and cagA+ status determined by polymerase chain reaction (PCR). RESULTS: There was no significant difference (P = 0.784) in mean mucus thickness between cagA+ (52.7 +/- 1.2 microm, n = 10), cagA- (46.6 +/- 1.1 microm, n = 18) or H. pylori-negative patients (51.3 +/- 1.1 microm, n = 30). In cagA- patients, mucus thickness was significantly reduced with increased H. pylori colonization density, Spearman (r(s)) = -0.805, P < 0.0001. In contrast, in cagA+ patients there was a weak positive, but not significant, association between mucus thickness and H. pylori colonization density, r(s) = 0.333, P = 0.381. CONCLUSIONS: The human gastric mucus thickness is not affected by infection with cagA+ or cagA- strains of H. pylori compared with uninfected. Although a trend of increased mucus thickness with cagA+ infection was observed.

Human gastric mucosal hydrophobicity does not decrease with Helicobacter pylori infection or chronological age.

BACKGROUND AND AIMS: Infection with cytotoxin-associated gene A (cagA) Helicobacter pylori is associated with severe gastric diseases. Previous studies in humans have reported a decreased gastric hydrophobicity with H pylori infection. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus hydrophobicity. METHODS: One hundred patients without peptic ulcers and not on medication were randomly recruited from endoscopy clinics; each patient had six biopsies. Contact angle measurements were performed using a goniometer assisted by computer software. H pylori status was assessed by histology, Campylobacter-like organism test and culture, and cagA+ status was determined by polymerase chain reaction. RESULTS: In age- and sex-matched patients, there was no significant difference (P=0.27) in contact angle between H pylori-positive (61+/-2.8 degrees ) and H pylori-negative patients (65.5+/-3.0 degrees ). There was also no significant difference (P=0.36) in contact angle among H pylori-negative, cagA- and cagA+ patients (65.5+/-3.0 degrees , 58.6+/-3.6 degrees and 63.4+/-4.9 degrees , respectively). However, a trend of increased mean contact angles in cagA+ compared with cagA- and H pylori-negative patients was observed in patients 50 years and younger (68.3+/-8.3 degrees , 61.1+/-6.1 degrees and 63.6+/-2.2 degrees , respectively; P=0.70) and in patients without atrophy (71.1+/-8 degrees , 59.6+/-4 degrees and 66+/-2 degrees , respectively; P=0.30). In addition, there was no significant correlation between contact angles and patient age (r=0.104, P=0.306). CONCLUSIONS: The present study shows that H pylori infection and the chronological age have no effect on the gastric mucus hydrophobicity, but it highlights a trend of increased mucus hydrophobicity with cagA+ infection that needs to be supported by future studies.

The association between cagA+ H. pylori infection and distal gastric cancer: a proposed model.

Cytotoxin-associated gene A (cagA)+ infection is associated with an increased risk of distal gastric cancer. The aim was to determine the effect of Helicobacter pylori (HP) on gastric mucus thickness, hydrophobicity, and PGE2 and their relation to colonization density. Ninety-nine patients were recruited (69 HP- and 30 HP+: 10 cagA+, 18 cagA-, 2 undetermined) and six biopsies were obtained from each patient. Mucus thickness, hydrophobicity, PGE2, and colonization density were determined. HP status was assessed by histology and culture; cagA+ was determined by PCR. In age- and sex-matched patients, PGE2 was greater in PH+ than HP- (P = 0.04), with cagA+ having higher PGE2 than HP- patients (P = 0.031). No differences were observed in mucus thickness (P = 0.717) or hydrophobicity (P = 0.27) between HP+ and HP- patients. However, cagA+ showed a nonsignificant trend of increase in mucus thickness (P = 0.784) and hydrophobicity (P = 0.30) compared to cagA- and HP- patients. cagA+ colonization density was weakly correlated with increased thickness (r = 0.333, P = 0.381), whereas cagA- density was inversely correlated with thickness (r = -0.805, P = 0.0001). A model suggesting the possible changes induced by cagA+ infection is proposed which explains the high association of cagA+ with distal gastric cancer. If supported by large multicenter studies, this could form the basis for the development of new therapies directed at the mucous layer to eradicate HP and thus reduce the risk of gastric cancer.

cagA+ Helicobacter pylori induces greater levels of prostaglandin E2 than cagA- strains.

cagA+ Helicobacter pylori (HP) infection is associated with an increased risk of distal gastric cancer. Previous studies investigating the effect of HP infection on prostaglandin E2 (PGE2) levels have not differentiated between cagA+ and cagA- strains and consequently have produced contradictory results. The aim was to investigate the effect of cagA+ strains on PGE2 and enhance the understanding of the mechanisms leading to gastric diseases. Hundred patients without peptic ulcers and not on medication were recruited (one later excluded) from endoscopy clinics: six biopsies were obtained from each patient. PGE2, colonization density and histology were determined. In addition, HP status was assessed by histology, CLOtest and culture with cagA+ being determined by PCR. Sixty-nine patients were HP- and 30 HP+ (10 cagA+, 18 cagA-, 2 undetermined). In age and sex-matched patients, PGE2 was significantly greater (P = 0.04) in HP+ (37.2 +/- 1.2 pg/mg per 20 min) than in HP- (22.6 +/- 1.2). In patients without atrophy, those infected with cagA+ had significantly higher (P = 0.03) PGE2 levels (53 +/- 1.1) than HP- patients (22.6 +/- 1.1) and greater levels (P = 0.29) than cagA- patients (35 +/- 1.3). In conclusion, the increased levels of PGE2 in the presence of cagA+ infection could be an important factor by which cagA+ strains enhance the gastric mucus layer protective functions leading to established colonization, gastritis and increased risk of gastric cancer. However, further evaluation with a large-scale multi-centre study is required to substantiate this hypothesis.