Background-It has been proposed that a pathogenic eVect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial. Aims-To clarify the eVects of H pylori infection on the mucus gel barrier in vivo.Methods-Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pylori infection. Results-There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness between H pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) µm, 106 (30) µm respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) µm, p=0.03) compared with those without atrophy. Conclusions-A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insuYcient to cause a collapse of the mucus barrier. (Gut 1998;43:470-475) Keywords: Helicobacter pylori; gastric mucus Helicobacter pylori infection leads to gastritis and is an aetiological factor in the pathogenesis of peptic ulceration.1 H pylori is located within the adherent mucus barrier, particularly in the region of the gastric pit, close to the mucosal surface.2 The mucus barrier, together with epithelial bicarbonate secretion, is considered to be the first line of mucosal defence against acid and pepsin.3 This mucus layer also provides a protective environment for H pylori to colonise. 4 However, it is controversial whether or not H pylori colonisation results in changes in mucus structure and production, thereby impairing its protective eYcacy.A weakening of the mucus barrier by H pylori, leading in some cases to its collapse, has been proposed, based on the demonstration in vitro of a mucolytic proteinase in filtrates from cultures of H pylori.5 6 However, other groups have failed to show significant amounts of proteinase activity in either culture filtrates or extracts of H pylori.7-9 A non-proteolytic, urea dependent breakdown of the mucus gel by filtrates of H pylori has been observed and explained by urease activity producing ammonium ions which disrupted mucus lipid interactions.8 A study in vivo looking at mucus gel in gastric washouts, but not from the adherent mucus gel barrier, showed that mucus viscosity from H pylori infected subjects was not reduced compared with that from noninfected subjects.10 One study in vivo, observing unfixed sections of gastric mucosal biopsy specimens, showed an up to 50% reduction in mean mucus thickness of the adherent mucus gel barrier in patients with H pylori infection, compared with non-infected controls.11 Recently decreased expression of MUC5AC and aberrant expression of the glandular mucin MUC6 in gastric epithelial cells has been shown to occur with H pylori in...

The proinflammatory cytokine interleukin-1 has been implicated in host susceptibility to Helicobacter pylori-associated disease. Recent studies suggest that this susceptibility may be under genetic control. It remains to be determined whether the relationship between IL-1 gene polymorphism and gastrointestinal disease in patients with H. pylori infection is due to the role of IL-1 in determining susceptibility to H. pylori infection per se or to the development of distinct pathological lesions. The aim of this study was to prospectively investigate the relationship between selected polymorphisms in three of the major IL-1 gene family members, seeking associations with H. pylori infection and/or gastric cancer. A total of 559 individuals were studied: 191 patients attending for gastroscopy, 98 with current or previous H. pylori, an additional 79 patients with gastric cancer, and 289 healthy controls. The major novel finding of the study was a marked difference in the genotype frequencies for the IL1R1 Hinfl SNP in those with current or previous evidence of H. pylori compared to those without. (GG, 53 vs 75%; GA, 40 vs 19%; AA, 7 vs 6%; P = 0.0079). The association indicates an increased risk of H. pylori infection or persistence in those with the IL1R1 Hinfl A allele (0.27 vs 0.156; P = 0.009; OR = 2.01). Our results suggest that the relationship among IL-1 gene polymorphism, H. pylori, and disease is more complex than initially proposed. More detailed studies of the IL-1 gene cluster are needed.