Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Inflammatory bowel disease (IBD), including Crohn's disease and Ulcerative Colitis, is associated with significant alterations in the gut microbiome.
• The role of specific microbial components, such as lipopolysaccharides (LPS) from Gram-negative bacteria, in driving intestinal inflammation in IBD remains incompletely understood.

Purpose of the Study:

• To investigate the differential pathogenic potential of lipopolysaccharides (LPS) from five key Gram-negative bacterial species altered in IBD.
• To evaluate the impact of serotype-specific LPS on resident intestinal cells and barrier function.

Main Methods:

• Stimulation of HEK-TLR4 cells with LPS from five distinct Gram-negative bacterial species to assess NF-κB and IL-8 induction.
• Exposure of human colonic epithelial cell monolayers (Caco-2) to serotype-specific LPS to measure inflammatory mediator production (TNF-α, IL-10).
• Assessment of Caco-2 monolayer permeability changes, including trans-epithelial electrical resistance (TEER), small molecule flux, and tight junction integrity.

Main Results:

• LPS from different bacterial species exhibited varying capacities to induce NF-κB and IL-8 production in a TLR4-dependent manner.
• Caco-2 cells demonstrated distinct inflammatory mediator profiles in response to serotype-specific LPS.
• Serotype-specific LPS differentially modulated intestinal epithelial barrier function, affecting TEER, molecule transport, and tight junction integrity.

Conclusions:

• Specific Gram-negative bacterial species, via their unique LPS, may contribute to the pathogenesis of IBD and other chronic inflammatory conditions.
• The findings highlight serotype-specific LPS-mediated inflammatory responses and barrier disruption as potential mechanisms in IBD.