The article discusses the fundamental nature of inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease. Two main hypotheses are considered: one focuses on the dysregulation of the mucosal immune system leading to excessive responses to normal gut microflora, while the other highlights changes in gut microflora composition or impaired epithelial barrier function that trigger pathological immune responses. The authors conclude that IBD is characterized by an abnormal mucosal immune response, which can be facilitated by microbial factors and epithelial cell abnormalities. They review evidence supporting both hypotheses, including studies on the role of innate immune factors, the impact of specific bacterial components, and the significance of the epithelial barrier. The article also discusses emerging therapies for IBD, emphasizing the need to understand the molecular defects and their functional impact on mucosal immune responses and epithelial cell barrier function.The article discusses the fundamental nature of inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease. Two main hypotheses are considered: one focuses on the dysregulation of the mucosal immune system leading to excessive responses to normal gut microflora, while the other highlights changes in gut microflora composition or impaired epithelial barrier function that trigger pathological immune responses. The authors conclude that IBD is characterized by an abnormal mucosal immune response, which can be facilitated by microbial factors and epithelial cell abnormalities. They review evidence supporting both hypotheses, including studies on the role of innate immune factors, the impact of specific bacterial components, and the significance of the epithelial barrier. The article also discusses emerging therapies for IBD, emphasizing the need to understand the molecular defects and their functional impact on mucosal immune responses and epithelial cell barrier function.