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

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• Anti-tumor necrosis factor alpha (TNF-α) therapies are common for inflammatory bowel disease (IBD), but their effectiveness varies and often decreases over time.
• Novel therapeutic approaches are required due to the limitations of current IBD treatments.

Purpose of the Study:

• To investigate if Lactobacillus murinus (L. murinus) can reduce TNF-α-induced inflammatory responses in an in vitro model of human intestinal colitis.
• To explore the role of the aryl hydrocarbon receptor (AHR) in mediating the effects of L. murinus.

Main Methods:

• An in vitro colitis model was created using Caco-2 intestinal cells stimulated with TNF-α.
• Cells were pre-treated with L. murinus or AHR ligands.
• Effects on AHR activation, barrier integrity (measured by TEER), and IL-8 secretion were assessed.
• CYP1A1 mRNA expression, an AHR target gene, was measured as a marker of AHR modulation.

Main Results:

• TNF-α significantly impaired epithelial barrier function and increased IL-8 secretion.
• L. murinus pre-treatment increased CYP1A1 expression and attenuated TNF-α-induced barrier damage and IL-8 release.
• Synthetic AHR ligands did not replicate the protective effects of L. murinus, indicating ligand-specific AHR responses.

Conclusions:

• L. murinus may mitigate TNF-α-induced gut inflammation and barrier dysfunction through AHR signaling.
• This study highlights a potential probiotic mechanism for IBD treatment.
• Further research is needed to confirm AHR dependency and identify specific L. murinus metabolites involved.