Humans have coevolved with the microbial communities that colonize them, resulting in an intricate and complex assembly of thousands of microbial species living mutualistically in their gastrointestinal tract. Establishing from birth, the resulting and dynamic gut microbiota has a collective proximal and systemic impact on the entire human body and physiology. Gut microbes are affected by numerous factors such as diet, medication, or host genetics, but also in turn can affect the balance of circulating metabolites, influencing health and disease outcomes. Furthermore, it has recently emerged that the commensal microbiota could also interact both positively or negatively with infection from pathogens (and the spread of their associated antimicrobial resistance genes), which could play an important yet unclear role on non-communicable and infectious disease risk and progression. Our interdisciplinary team has a successful history of: (a) microbiome and host-microbe interactions, (b) disease prediction analysis, including ML approaches, and (c) pathogen genomics and bioinformatics, most of which leveraging large human population multi-omics datasets. Here, we propose an integrated project consisting of three main related objectives to explore the role of the gut microbiome and circulating plasma metabolome and proteome on pathogenic carriage and on infectious and non-communicable disease risk and progression. We request multiple datasets and variables from the SIMPLER cohort to achieve this 5-year project along this detailed plan and aims below.