The crucial biological functions of the human microbiome in health are currently being investigated with metagenomic approaches that sequence whole microbial communities from in vivo samples. The involvement of the microbiome in autoimmune diseases has been proven, and the technological transition to the second generation community-wide full-genome shotgun sequencing is potentially enabling deeper, mechanistic, and functional microbiome profiles. However, the full potential of shotgun sequencing is currently unexpressed because effective methods to analyse the produced data are missing and only few partial hypothesis-driven datasets are available. The goal of CoMeMIMP is to make a multidisciplinary breakthrough in both the analysis of shotgun metagenomic data and in the understanding of (i) the role of the human microbiome during infection and (ii) the vertical sources of the microbial and probiotic diversity in the colonizing infant gut microbiome. On the methodological aspect, I already developed the fastest and most accurate taxonomic profiling methods available, and we will fully express here the potential of metagenomic data with unprecedented strain-level resolution for all domains of life, phylogenetic/phylogenomic structure mining, and statistical predictive tools. This will have a major research impact and will provide us with invaluable additional power to address the specific hypothesis that the microbiome dictates the acquisition and severity of infections from opportunistic pathogens, and to accurately track the mother-to-infant vertical transmission of transient and resilient commensal microbiomes. We will produce and analyse metagenomic longitudinal datasets including both the microbiome and pathogen isolates in patients with cystic fibrosis, and a comprehensive map of microbial transmission from the human milk microbiome and skin to the developing infant gut microbiome paving the way to new therapeutic and probiotic intervention strategies.