Lactobacillus casei prevents impaired barrier function in intestinal epithelial cells

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• Epithelial barrier dysfunction contributes to various gastrointestinal diseases.
• The precise mechanisms by which probiotics influence intestinal epithelial barrier integrity remain incompletely understood.
• Cytokines like tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) are known inducers of epithelial barrier dysfunction.

Purpose of the Study:

• To investigate the role of the probiotic Lactobacillus casei in preventing cytokine-induced epithelial barrier dysfunction in intestinal epithelial cells (IECs).
• To elucidate the signaling pathways involved in the protective effects of L. casei.

Main Methods:

• Caco-2 intestinal epithelial cells were cultured and stimulated with TNF-α or IFN-γ.
• Lactobacillus casei was administered prior to cytokine challenge.
• Transepithelial electrical resistance (TER) and paracellular permeability were measured.
• Expression and distribution of tight junction protein zonula occludens-1 (ZO-1), p-Akt, and toll-like receptor 2 (TLR2) were analyzed using immunofluorescence and Western blotting.
• Mitogen-activated protein kinase (MAPK) inhibitors were used to probe signaling pathways.

Main Results:

• TNF-α and IFN-γ significantly impaired epithelial barrier function, indicated by decreased TER, increased permeability, and altered ZO-1 expression.
• Pretreatment with Lactobacillus casei effectively reversed these cytokine-induced barrier defects.
• The protective effects of L. casei were dependent on the MAPK signaling pathway, as inhibition abrogated the reversal of dysfunction.
• L. casei administration led to increased expression of TLR2 and phosphorylated Akt (p-Akt).

Conclusions:

• Lactobacillus casei demonstrates a significant protective effect against cytokine-induced epithelial barrier dysfunction in intestinal epithelial cells.
• The probiotic's action is mediated, at least in part, through the MAPK signaling pathway.
• Increased expression of TLR2 and p-Akt by L. casei contributes to the maintenance of intestinal barrier integrity.