Microbiome Core, Summary Mounting evidence indicates a strong association between the microbiome and immune development in early life (IDEAL). More specifically, we and others are providing growing evidence for a role of the microbiome in the three clinical outcomes targeted in this IDEAL proposal: vaccine response, respiratory infection, and asthma. In support of the proposed IDEAL program, the Microbiome Core (MBC) will generate and analyze shotgun metagenomes from 1300 nasal and fecal samples from the existing Rochester Combined Cohort (RCC) and the prospective Rochester IDEAL Cohort (RIC). Data generation and analyses will be conducted with rigorous quality assurance measures. The microbiome data, paired with clinical and other omic data, will be exceptional for an IDEAL study, and the nasal metagenomes will be unprecedented in scope and depth of microbiome coverage. The premise at the foundation of the MBC is that the microbiome is a key driver of IDEAL. As a consequence, we hypothesize that the microbiome will contribute to key objectives of the overall IDEAL proposal, (i) early prediction of clinical phenotypes, (ii) delineation of molecular endotypes among the phenotypes, and (iii) identification of actionable therapeutic targets. Further, comparative analysis of microbiomes will provide mechanistic insight to interactions between the microbiome and IDEAL. The MBC has two Specific Aims: SA1 is to generate microbiome data products, (i) high-quality shotgun metagenome sequence data, (ii) taxonomic profiles, and (iii) functional profiles. The data products will be transferred to the Data Management Core (DMC) to support Projects (PR) 1-3 in addressing the above key objectives. SA2 is microbiome analysis using both taxonomic and functional profiles, focussing on diversity, differential abundance, temporal dynamics, and interactions. The main purpose of the MBC analyses will be ecological and mechanistic interpretation of microbiome variability among the clinical phenotypes and molecular endotypes.