Core Viewpoint - The research published in Science reveals a novel Aeromonas variant (MTB) that produces aerolysin, which damages intestinal macrophage barriers and drives the occurrence of ulcerative colitis (UC), providing new insights into the etiology, diagnosis, and treatment strategies for UC [4][9]. Group 1: Mechanism of Ulcerative Colitis - Ulcerative colitis (UC) is a multifactorial disease involving immune dysregulation, genetic susceptibility, abnormal inflammatory responses to gut microbiota, and environmental factors [3]. - The study identifies that the function of resident macrophages in the intestines of UC patients is impaired, leading to compromised epithelial integrity [6]. - The depletion of macrophages occurs prior to the onset of visible inflammation, suggesting a critical role of these cells in maintaining gut health [6]. Group 2: Discovery of Aeromonas sp. MTB - The research team discovered a macrophage-toxic variant of Aeromonas, named Aeromonas sp. MTB, which expresses the virulence factor aerolysin [7]. - Macrophages exhibit higher sensitivity to cell death induced by aerolysin compared to epithelial cells, leading to barrier dysfunction without directly damaging epithelial cells [7]. - The presence of MTB in UC patients' fecal samples was significantly higher compared to healthy controls, indicating its potential role in UC pathogenesis [9]. Group 3: Experimental Findings - In mouse models, the presence of MTB exacerbates colitis symptoms, resembling UC, particularly in conditions of chemical or genetic macrophage depletion [8]. - Treatment with polyclonal anti-aerolysin antibodies can prevent MTB-induced colitis, while monoclonal antibodies can improve established colitis [8]. - The study emphasizes the microbial mechanisms promoting UC and suggests targeting bacterial virulence factors as a novel therapeutic strategy [9].