Fecal Microbiota Transplantation Attenuated Inflammation Through TGF-β1/Smad Signaling Pathway in Caco-2 and RAW264.7 Cells

Background/Aims: Ulcerative colitis (UC) represents a persistent inflammatory condition that influences millions of people worldwide,with rising prevalence and limited treatment options. Current therapies, such as corticosteroids and immunosuppressants, offer symptom relief but are associated with significant adverse effects. Fecal microbiota transplantation (FMT) is being increasingly viewed as an effective alternative, but the molecular basis for its benefits in UC is still not fully understood. This study aimed to explore the function of the transforming growth factor-beta 1 (TGF-β1)/Smad signaling cascade in FMT-induced remission of UC.

Materials and Methods: Stable Smad3-knockdown and Smad3-overexpression Caco2 cell lines were established via lentivirus-mediated transduction. These modified Caco-2 cells were co-incubated with RAW264.7 macrophages to mimic intestinal inflammation in vitro. Following FMT treatment, the expression of major components of the TGF-β1/Smad signaling cascade was assessed.

Results: The results demonstrated that FMT markedly downregulated TGF-β1, Smad2, and Smad3 expression, while enhancing Smad7 expression in both Smad3-knockdown and overexpression cell lines. In addition, FMT treatment attenuated the phosphorylation of Smad2 and Smad3, indicating a decrease in the activation of the TGF-β1/Smad signaling pathway.

Conclusion: These findings suggest that optimizing FMT protocols targeting this pathway could improve therapeutic outcomes for UC patients.

Cite this article as: Qiu J, Wu C, Li S, Yang X. Fecal microbiota transplantation attenuated inflammation through TGF-β1/Smad signaling pathway in Caco-2 and RAW264.7 cells. Turk J Gastroenterol. Published online October 10, 2025. doi:10.5152/ tjg.2025.25172.