Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function

Area of Science:

• Gastroenterology
• Microbiology
• Immunology

Background:

• Live probiotics are known to reduce gut permeability and inflammation.
• Probiotics release peptide bioactive factors that modulate epithelial resistance.
• The specific impact of Bifidobacteria infantis factors on intestinal epithelial cells and in vivo models requires further investigation.

Purpose of the Study:

• To determine the effect of factors from Bifidobacteria infantis (BiCM) on intestinal epithelial cell permeability and tight junction proteins.
• To assess if these factors retain bioactivity when administered to IL-10-deficient mice.
• To elucidate the role of MAP kinases in mediating these effects.

Main Methods:

• T84 human epithelial cells were treated with BiCM in the presence of TNF-alpha and IFN-gamma to assess Transepithelial Electrical Resistance (TER), tight junction protein expression (claudins, ZO-1, occludin), and MAP kinase activity (p38, ERK).
• Acute effects on colonic permeability were evaluated in IL-10-deficient mice using Ussing chambers.
• Long-term effects were assessed in IL-10-deficient mice treated orally with BiCM for 4 weeks, measuring histological injury, cytokine levels, and immune responses.

Main Results:

• BiCM increased TER, decreased claudin-2, and increased ZO-1 and occludin expression in T84 cells.
• BiCM prevented TNF-alpha and IFN-gamma-induced decreases in TER and tight junction protein disruption.
• ERK activation was crucial for BiCM's effects on TER and protection against inflammatory cytokines.
• Oral BiCM administration reduced colonic permeability in mice and attenuated inflammation, normalized permeability, and decreased IFN-gamma secretion in long-term treated IL-10-deficient mice.

Conclusions:

• Peptide bioactive factors from Bifidobacteria infantis retain their biological activity in vivo.
• These factors are effective in normalizing gut permeability and improving disease in an animal model of colitis.
• The therapeutic effects of BiCM are mediated, in part, by modulation of MAP kinases and tight junction proteins.