AIEC colonization and pathogenicity: influence of previous antibiotic treatment and preexisting inflammation

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Inflammatory bowel diseases (IBD) are linked to abnormal gut colonization by adherent-invasive Escherichia coli (AIEC).
• Mutations in the NOD2 gene impair the host's ability to clear intracellular bacteria, potentially affecting AIEC interactions.
• Understanding the interplay between antibiotic use, AIEC, and host genetics is crucial for IBD management.

Purpose of the Study:

• To investigate the impact of antibiotic treatment on AIEC colonization in wildtype (WT) and NOD2 knockout (NOD2KO) mice.
• To assess the consequences of AIEC colonization on intestinal inflammation in these models.
• To determine the role of NOD2 in AIEC persistence and translocation.

Main Methods:

• Mice (WT and NOD2KO) received antibiotic treatment followed by AIEC infection, with sampling at various time points.
• A separate cohort underwent dextran sodium sulfate (DSS) treatment followed by AIEC challenge to model colitis.
• AIEC colonization, mesenteric translocation, and inflammatory markers were quantified in ileum, colon, and mesenteric tissues.

Main Results:

• Antibiotic treatment was essential for AIEC colonization in both WT and NOD2KO mice.
• AIEC persisted longer in the ileum and colon of NOD2KO mice compared to WT mice.
• AIEC exacerbated DSS-induced colitis in WT mice, increasing clinical and histological inflammation.
• Mesenteric translocation of AIEC was observed exclusively in NOD2KO mice.

Conclusions:

• Antibiotic administration is a prerequisite for AIEC gut and mesenteric colonization.
• NOD2 plays a critical role in controlling AIEC persistence and preventing mesenteric translocation.
• AIEC can worsen pre-existing colitis, highlighting its pathogenic potential in IBD contexts.