Microbes are an integral part of our genetic landscape and essential for our health and well-being. In many diseases, such as chronic inflammatory bowel diseases, an imbalance of the human microbiome has been observed. The underlying reasons and consequences of these microbial imbalances are largely unknown though. Previous studies have identified important taxonomic changes of the microbiome, including disease-associated bacteria. However, the functional consequences of these taxonomic changes and how they impact the host are still largely unknown. To address these challenges, my lab uses integrated analyses of complex multi-omics datasets from large clinical cohorts, where we combine information from the host and the microbiome to computationally generate testable hypotheses on the functionality of the microbiome in disease. We combine these computational approaches with experimental validation of the immunogenicity and inflammatory activity of the identified bacterial strains and metabolites, providing insights into the potential mechanisms of the human microbiome in health and disease.