Probiotic-derived polyphosphate improves the intestinal barrier function through the caveolin-dependent endocytic...

Area of Science:

• Microbiology
• Cell Biology
• Immunology

Background:

• Probiotics offer health benefits by maintaining host homeostasis.
• The specific mechanisms of probiotic-host interactions are not fully understood.
• Bacterial polyphosphates (poly P) are known to influence host cells.

Purpose of the Study:

• To elucidate the cellular uptake mechanism of Lactobacillus brevis-derived polyphosphate (poly P).
• To investigate the role of host cell pathways in mediating poly P's beneficial functions.
• To identify downstream molecular targets of poly P involved in host protection.

Main Methods:

• Immunostaining of Caco2/bbe cells to visualize poly P uptake.
• Inhibition assays using integrin β1 and caveolin-1 blockers.
• High-throughput sequencing to analyze gene expression changes.
• Assessment of intestinal barrier function and HSP27 induction.

Main Results:

• Poly P uptake is mediated by integrin β1 and caveolin-1 in lipid rafts.
• Inhibition of caveolin-1 suppressed poly P's functional effects, indicating endocytic pathway involvement.
• Poly P induced tumor necrosis factor alpha-induced protein 3 (TNFAIP3), promoting cytoprotection and barrier function.
• This interaction is independent of pattern recognition receptor pathways.

Conclusions:

• Lactobacillus brevis poly P is internalized into host cells via a caveolin-1 dependent endocytic pathway.
• The uptake and subsequent functions of poly P are crucial for enhancing intestinal barrier integrity.
• This study reveals a novel mechanism of host-probiotic interaction involving direct bacterial substance internalization.