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Scientific evidence that supports a correlation between our intestinal microbiota and health status has caused significant interest in microbe-host interaction studies. It has generated a paradigm shift from analyzing pathogens to that involving commensal and probiotic bacteria. This review summarizes the interaction mechanisms described for Lactobacilli and Bifidobacteria based on recent omics-based developments. This information is expected to provide new avenues for further unravelling the set of interactions that includes the interactome of microbial and host cells.