Helicobacter pylori is well adapted to the harsh environment of the human stomach, allowing it to persistently colonize the gastric mucosa of at least 50% of the global population for decades. Long-term colonization induces chronic inflammation that can eventually lead to development of peptic ulcer and gastric cancer. The interaction between host, bacterial and environmental factors are crucial for the pathogenesis of H. pylori. In contrast, Lactobacillus species are members of the human microbiota and act as a first line of defense against pathogens. However, the underlying mechanisms behind lactobacilli-mediated pathogen inhibition still need further investigation.

This thesis focuses on understanding the interplay between commensal and pathogenic bacteria with the human host. In Paper I, we investigated the effect of different Lactobacillus strains on the initial attachment of H. pylori to gastric epithelial cells and found that certain Lactobacillus strains can prevent the adhesion of the pathogen by decreasing the expression of SabA. In Paper II, the anti-inflammatory activity of Lactobacillus strains against H. pylori-induced production of proinflammatory cytokines was explored. We demonstrated the ability of L. gasseri Kx110A1 to reduce the level of TNF and IL-6 in human macrophages through suppression of ADAM17, a metalloproteinase responsible for releasing transmembrane proteins. Lactobacilli-mediated inhibition of these cytokines was not H. pylori-specific, suggesting a general anti-inflammatory property of L. gasseri Kx110A1. In Paper III, we characterized the role of sortase-dependent proteins in L. gasseri Kx110A1. We showed that the deletion of sortase A in lactobacilli resulted in the reduction of auto-aggregation and attachment to host gastric epithelial cells. Moreover, sortase A mutant lactobacilli were not effective in preventing H. pylori initial adherence. Finally, in Paper IV, we showed that lactate can affect the expression of H. pylori adherence genes and the production of bacterial-induced proinflammatory cytokines.