**3. Pathogenesis of functional dyspepsia associated with** *H. pylori* **infection**

The pathophysiological disturbances generally responsible for the dyspepsia focus on hyperacidity, impaired gastric accommodation (the "stiff fundus") and delayed gastric emptying. FD patients who are infected with *H. pylori* have higher stimulated gastric acid secretion than *H. pylori*-negative healthy volunteers. [16] Impaired accommodation to a meal may be common in functional dyspepsia and early satiety, but is not particularly associated with *H. pylori* positivity or delayed gastric emptying. There is no constituent disturbance of sensory or motor function yet reported in H. pylori-infected persons. Another factor possibly responsible for the dyspepsia associated with H. pylori infection is the gut hormone, ghrelin. Secreted from oxyntic cells, ghrelin normally stimulates gastric motility and food intake. Patients with *H. pylori* may have reduction in ghrelin secretion that might lead to impaired gastric emptying and symptoms of postprandial dyspepsia.

Recent study demonstrated that metronidazole resistant strains of *H. pylori* infection were significantly higher in PDS than those of EPS patients. This study also indicated more specific of *cagA* genotype that presence of *cagA 2a* gene of *H. pylori* infection was significantly higher in metronidazole resistant than those of metronidazole sensitive strains especially in EPS patients. This finding might be helpful to identify metronidazole resistant by using *cagA* genotype in dyspeptic patients. [17]

*CagA* is a highly immunogenic protein encoded by the *cagA* gene, located at end of the *cag* pathogenicity island (PAI). Infection with *cagA*-positive strains was associated with a greater inflammatory response and an increased risk of adverse clinical outcomes than with *cagA*negative strains. [7, 18-20] Taneike et al recently reported that the metronidazole resistant rate in *cagA* negative group was significantly higher than in *cagA* positive group and suggested that absence of *cagA* might be a risk factor in development of metronidazole resistance. [21] Unlike many countries such as European countries and United State of America, nearly all of *H. pylori* strains in Thailand possess *cagA*-positive strains. [16] These different results might be explained by variation in *cagA* between the Asian- and Western-types. *CagA* genotype can be divided into *cagA 1a* and *2a* [17] and *cagA 1a* strain of *H. pylori* demonstrated more virulence and associated with more gastric inflammation due to activation of proinflammatory cytokines such as increased production of IL-1β and IL-8 in the gastric mucosa. [21] Previous metaanalysis study reported that *cagA*-positive strain increases the likelihood of successful eradication. [22] The mechanism for the effect of *cagA* on eradication outcome might be explained by the presence of *cagA* induces secretion of inflammatory cytokine in gastric epithelial cells and increased gastric inflammatory response. [22] Consequently, the increase blood flow may help in the diffusion of antibiotics. [23] Another possibility might be explained by the density of *H. pylori* in gastric mucosa which has been reported to be higher in *cagA*positive strains than *cagA*-negative strains, thus *cagA*-positive strains might be proliferative faster than *cagA*-negative strains. [24, 25] As antibiotics are more active on rapidly growing bacteria, *cagA*-positive strains would be more susceptible to antibiotic activity [23].

The effect of *H. pylori* eradication on dyspeptic symptoms in FD patients has revealed incon‐ clusive results in several studies, both in developed countries and in Asia. [26, 27, 28, 29] Dyspeptic patients who are infected with *H. pylori* often have functional dyspepsia rather than peptic ulcer disease, yet the outcome of eradicating *H. pylori* infection may be suboptimal in FD compared with that for established duodenal ulcer disease. [30] Nevertheless, at a popu‐ lation level, a Cochrane systemic review indicated that there was a 10% relative risk reduction of persistent symptoms in the *H. pylori*-eradication group compared to placebo; the number needed to treat to cure one case of dyspepsia was 14. [31] A recent meta-analysis of the Chinese literature showed that dyspepsia symptoms in FD improved after *H. pylori* eradication with an odds ratio of 3.61, suggesting that this infection might have a greater role in Asian than in Western countries. [32] Thus, *H. pylori* eradication overall does improve dyspepsia, particu‐ larly in regions with high prevalence.
