While different diseases are linked with different interactions between the microbiome and the host, key areas of investigation remain. These include understanding the microbiome's treatment response, metabolic consequences, underlying molecular pathways, and identifying microbiome components that enhance clinical status. To illustrate the need of microbiome studies and the microbial effectors, we present the following four clinical use cases: (i.) Recent studies have shown that microbial proteins, which accumulate under specific conditions, as well as their sequence diversity, structural features, and post-translational modifications (PTMs) like acetylations, deaminations, hydroxylations, methylations, nitrosylations, oxidations, and phosphorylations, are critical for priming immune cells effectively . Understanding these variations in proteins, whose nature can be revealed through metaproteome analysis, combined with advanced computational methods such as protein structure prediction [117] and all-atom molecular dynamics (MD) simulations , provides insights into the role of microbial proteins in immune regulation. This insight could potentially guide the development of targeted therapeutic strategies.