Ulcerative colitis (UC) is characterized by disruptions of the gut microbiome and an exaggerated mucosal immune response in genetically susceptible individuals. Alterations in the composition of the intestinal metabolome associated with dysbiosis can trigger chronic inflammation. However, it remains unclear whether microbial dysbiosis is the cause or consequence of chronic mucosal inflammation. To address this gap, we aimed to investigate the potential pro-inflammatory effects of sterile fecal microbiome filtrate (FMF) using a microphysiological, immunocompetent intestine-on-chip (IoC) model.