Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 16 1 2024 02 12 79 89 EN Alireza Moulazade Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Sara Soudi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Bita Bakhshi Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2023 09 25 2023 12 06 Background and Objectives: Mesenchymal Stem Cells (MSCs) can repair gastrointestinal tract damage. The Secretome of MSCs has a high capacity to inhibit bacterial colonization and the subsequent inflammatory responses of Vibrio cholerae. Materials and Methods: The Caco-2 cells were treated with adipose-derived MSCs (AD-MSCs) secretome and then infected with V. cholerae. Subsequently, the bacterial attachment and invasion, cholera toxin gene expression, PGE2 and IL-6 secretion, TNF-α, IL-1β, and IL-8 expression, and apoptosis of Caco-2 cells were evaluated. Results: The secretome of AD-MSCs significantly reduced the V. cholerae attachment and internalization on Caco-2 epithelial cells (P<0.0001). The cholera toxin (Ctx-B) gene expression (FR=4.56 ± 0.66) and PGE2 production (P=0.0007) were also significantly reduced. The production of NO and TNF-α, IL-1β, and IL-8 pro-inflammatory cytokines were significantly (P<0.05) reduced in exposure to the secretome of AD-MSCs. Secretome also improved a significant 81.33% increase in IL-6 production (128.1 ± 37.6 pg/mL) and showed a 12.36% significant decrease in epithelial cell apoptosis (P< 0.0001) after exposure to V. cholerae. Conclusion: The secretome of AD-MSCs can play a critical role in inhibiting bacterial colonization, and subsequent inflammatory responses, and maintaining the integrity of the epithelial barrier. The secretome may be effective in the prevention of hypovolemic shock. https://ijm.tums.ac.ir/index.php/ijm/article/view/4412 https://ijm.tums.ac.ir/index.php/ijm/article/download/4412/1640