Bacteroides and Phocaeicola spp. can colonize the human gut after birth and are reaching high abundances in the human adult microbiota. They are members of a healthy microbiota, but are also implicated in several diseases, such as inflammatory bowel diseases (IBD), Graft versus Host Disease (GvHD), cancer, infections and obesity. Increased abundances of Bacteroides and Phocaeicola spp. in IBD patients has been frequently reported, where P. vulgatus is explicitly highlighted as a pathobiont and recent evidence links its proteolytic properties to ulcerative colitis (UC) pathogenesis. However, the genomic plasticity and adaptive capacity of disease-relevant strains and the selective contribution of specific gene functions of P. vulgatus to the complex regulation of intestinal health are still largely missing. In this project, we will focus on the functional adaptation of Phocaeicola vulgatus to host-related metabolic changes and inflammatory conditions in the intestinal milieu and investigate how this adaptation contributes to the initiation and progression of IBD. For this, we will identify genomic, transcriptional and translational adaptation mechanisms ex vivo and in vivo and will identify functional consequences of this adaptation to disease initiation (metabolic injury) and progression (inflammation). Our goal is to identify functionally relevant adaptive gene targets of P. vulgatus, which are causally involved in the initial and progressive pathogenesis of IBD.