The forefront of the gastrointestinal mucosa consists mainly of a continuous polarized epithelial monolayer, protected by mucus. This strong defense barrier can be colonized by pathogens that trigger acute and chronic inflammation. This exceptional colonization ability is associated with an increased risk of developing adenocarcinomas at the sites of infection. Indeed epidemiological studies have described a strong correlation between the chronic infection with Helicobacter pylori and gastric cancer as well as a correlation between Salmonella enterica carriage and the onset of gallbladder cancer. Considering the epithelium as center court for infection, inflammation and cancer we have regenerated the epithelial monolayers of the gallbladder and of the human gastric mucosa in vitro. The infection of these human primary cell models reveals novel insight into bacterial induced host genotoxicity, inflammation and epithelial defence mechanisms.