**Acknowledgements**

characteristics of *H. pylori*. Strains that are also positive for both *homB* and *jhp562* are related to a higher risk of paediatric peptic ulcer disease. Thus, it is likely that these new markers acting together with the well-established virulence markers will promote a more severe antral

Other pathogenic genes interact synergistically to induce peptic ulcer in young patients. There is no gene or protein that acts alone to establish the virulence of *H. pylori* [74]. Accordingly, we investigated further virulence-associated genes by comparing the proteome of a group of genetically/epidemiologically-unlinked *H. pylori* strains, all isolated from Portuguese children, half suffering with peptic ulcer disease, and the other presenting only active gastritis [16]. Despite the typical proteome profile of all the *H. pylori* strains grown under the same labora‐ torial conditions [129], the ulcerogenic paediatric *H. pylori* strains presented differences suggestive of higher motility, better antioxidant defences and a metabolism favouring the biosynthesis of aromatic amino acids. As already mentioned in this chapter (see section 1.2.1 of this chapter) motility is a long known virulence-related trait [46], with lower-motility associated reduced inflammation levels [47] and with non-motile strains unable to establish a robust infection [42,45,46]. Moreover, it was more recently shown that higher motility enhances

The differences in the abundance of antioxidant proteins observed between paediatric ulcerogenic and non-ulcerogenic strains may be important in conferring resistance to inflam‐ mation; the enzymes involved in key steps in the metabolism of glucose, amino acids and urea

Additionally, by comparing the duodenal ulcer-associated paediatric strains with the one studied strain associated with gastric ulcer, we observed differences on the abundance of proteins associated with acid resistance and motility. These suggest that the former are better prepared to survive to the abnormal low levels of pH observed in duodenal ulceration, in contrast to the gastric ulcer strain which is a better swimmer, supporting the proximal spread of infection characteristic of this disease [16]. Overall, our data supports the idea that the infecting strain may be determinant in the divergence between duodenal and gastric ulcer [93].

The prevalence of *H. pylori* infection remains high worldwide despite a progressive decline over time, attributed to improved overall living conditions and hygiene. Although often asymptomatic, most infected patients suffer from persistent non-ulcer dyspepsia that, usually later in adulthood, may further progress to more severe conditions. The most common severe complication *H. pylori* is duodenal ulcer, affecting 10 to 15% of the infected adults. Although less frequent, 2 to 5% of the infected adults with non-ulcer dyspepsia progress to gastric ulceration and some ultimately to gastric cancer. These two forms of peptic ulcer-related (organic) dyspepsia differ in prevalence and physiopathology; those suffering with duodenal ulcer are at low risk of developing a gastric ulcer/gastric cancer. The onset of peptic ulcers in childhood is a rare event that may occur shortly after infection, suggesting more virulent *H.*

inflammation, a phenomenon strongly associated with duodenal ulceration.

82 Dyspepsia - Advances in Understanding and Management

*H. pylori* density and inflammatory response in dyspeptic patients [130].

may be advantageous to respond to fluctuations of nutrients [16].

**2. Conclusions**

This work was supported by BNP Paribas patronage and a research Grant from the Sociedade Portuguesa de Gastrenterologia.
