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Helicobacter pylori is a bacterium that selectively infects the gastric epithelium of half of the world population. The microbiome, community of microorganisms gained major interest over the last years, due to its modification associated to health and disease states. Even if most of these descriptions have focused on chronic disorders, this review describes the impact of the intestinal bacterial microbiome on host response to Helicobacter associated diseases. Microbiome has a direct impact on host cells, major barrier of the gastro-intestinal tract, but also an indirect impact on immune system stimulation, by enhancing or decreasing non-specific or adaptive response. In microbial infections, especially in precancerous lesions induced by Helicobacter pylori infection, these modifications could lead to different outcome. Associated to data focusing on the microbiome, transcriptomic analyses of the eukaryote response would lead to a complete understanding of these complex interactions and will allow to characterize innovative biomarkers and personalized therapies.