Lactobacillus murinus Induces CYP1A1 Expression and Modulates TNF-Alpha-Induced Responses in a Human Intestinal Epithelial Cell Model

Anti-TNF-α therapy is widely used for inflammatory bowel disease (IBD), but response rates vary, and long-term efficacy declines in many patients. Given the limitations of existing treatments, novel therapeutic strategies are needed. This study investigates whether <i>Lactobacillus murinus</i> (<i>L. murinus</i>) attenuates tumor necrosis factor alpha (TNF-α)-induced pro-inflammatory responses in a human intestinal epithelial cell model of colitis by modulating the aryl hydrocarbon receptor (AHR). An in vitro model was established using Caco-2 cell monolayers treated with TNF-α to simulate intestinal inflammation. Cells were pre-treated with <i>L. murinus</i> or known AHR ligands, and the effects on AHR activation, barrier integrity, and inflammatory response were assessed via transepithelial electrical resistance (TEER) and IL-8 quantifications. As CYP1A1 is a well-established transcriptional target of AHR, its mRNA expression was used as a surrogate marker of AHR modulation in this model. TNF-α stimulation significantly disrupted epithelial barrier integrity and increased IL-8 secretion in a dose-dependent manner. <i>L. murinus</i> pre-treatment enhanced CYP1A1 expression and was associated with reduced TNF-α-induced barrier disruption and IL-8 secretion. Notably, the beneficial effects of <i>L. murinus</i> on epithelial integrity were not replicated by synthetic AHR ligands, suggesting ligand-selective differences in AHR related responses. These findings suggest that AHR-associated signaling induced by <i>L. murinus</i> may contribute to mitigation of TNF-α-induced epithelial barrier dysfunction and inflammation. This study identifies a potential probiotic-associated mechanism that warrants further investigation, including studies designed to establish a causal role of AHR dependency in the observed effects. In addition, future studies are needed to identify the specific <i>L. murinus</i> metabolites responsible for inducing CYP1A1 expression and activating the AHR pathway.