BAMBI: A novel regulator of intestinal epithelial integrity in the control of colitis and colon cancer progression.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease affects approximately 7 million individuals worldwide. Its pathogenesis involves genetic susceptibility, alterations in the gut microbiota, and immune system imbalance, with both innate and adaptive components contributing through aberrant cytokine signaling. The Transforming Growth Factor-β (TGFβ) pathway plays a central role in this context, controlling the differentiation of regulatory T-cells (Tregs) and Th17 lymphocytes within the intestinal mucosa. Given the importance of these populations in maintaining intestinal homeostasis, we investigated the role of the TGFβ inhibitor BAMBI (BMP and Activin Membrane-Bound Inhibitor) in UC progression. In addition, due to the increased risk of colorectal cancer associated with chronic intestinal inflammation, we evaluated the effects of genetic ablation of Bambi (BAMBI-KO) in chronic inflammation-associated colon cancer progression. BAMBI expression is predominantly localized in the colonic epithelium, and either its absence or pharmacological inhibition confers protection against Dextran Sodium Sulfate-induced colitis. Mechanistically, this effect is TGFβ-dependent, independent of immune suppression and is associated with enhanced epithelial cell renewal and improved barrier function. Moreover, chronic UC induction in BAMBI-KO mice results in reduced colorectal tumor multiplicity, size and severity. Collectively, these findings identify BAMBI as a critical regulator of intestinal homeostasis and a potential therapeutic target in colorectal disease.