Mucus blocks probiotics but increases penetration of motile pathogens and induces TNF-α and IL-8 secretion

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• The intestinal mucosal barrier, comprising mucus and innate immunity, defends against luminal bacteria.
• Dysfunction of the mucus layer and bacterial infiltration are implicated in intestinal inflammation and disease.

Purpose of the Study:

• To investigate host-bacterial interactions at the mucosal interface using a novel in vitro model.
• To determine the role of the mucus layer and bacterial motility in bacterial transmigration and host immune response.

Main Methods:

• Development of an in vitro coculture model simulating the intestinal mucosal barrier with luminal space, mucus, epithelium, and immune cells.
• Utilized reconstituted porcine small intestinal mucus (880 ± 230 µm thick).
• Assessed transmigration of probiotic VSL#3 and pathogenic Salmonella (wild-type and flagella knockout) across the barrier, measuring immune cell differentiation and cytokine (IL-8, TNF-α) secretion.

Main Results:

• Mucus significantly reduced transmigration of nonmotile probiotic bacteria.
• Pathogenic Salmonella exhibited increased transmigration and induced higher levels of IL-8 and TNF-α in the presence of mucus.
• Nonmotile Salmonella (flagella knockout) showed reduced transmigration and lower induction of IL-8 and TNF-α.
• Increased bacterial transmigration correlated with immune cell differentiation and elevated pro-inflammatory cytokine concentrations.

Conclusions:

• Bacterial motility is a critical factor enabling pathogens to overcome the mucus barrier and transmigrate the intestinal epithelium.
• The in vitro coculture platform provides valuable insights into host-bacterial interactions at the mucosal interface.
• Understanding these interactions can inform improved therapeutic strategies for intestinal diseases.