Endogenous Ethanol-producing Bacteria Interference in Pathogen-host Crosstalk

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• The host micronutrient milieu, influenced by factors like vitamin B12, is crucial for immune defense.
• Ethanol and antibiotics can disrupt host-pathogen interactions by interfering with vitamin B12.
• The molecular mechanisms of how microbes affect host defense in the context of vitamin B12 competition are not fully understood.

Purpose of the Study:

• To investigate the interaction between Gram-positive ethanol-producing and Gram-negative vitamin B12-producing microbes.
• To explore how these microbes influence host cell defense biomarkers in response to infection.
• To understand the effects on absorbing, digesting, and defensive cells within the host milieu.

Main Methods:

• Co-cultured human colon (HT-29/B6) and liver (Huh7) cells were used.
• Cells were stimulated with Klebsiella pneumoniae (Kp52145) in the presence or absence of specific bacterial strains: Weissella confusa (ethanol-producing), Limosilactobacillus reuteri (B12-producing), or Pseudomonas nitroreducens (B12-producing).
• Key host defense biomarkers (MMP-1, lysozyme activity, ALP, IL-25) were measured post-stimulation.

Main Results:

• Kp52145 alone induced MMP-1, lysozyme, and ALP, while reducing IL-25.
• Pseudomonas nitroreducens potentiated MMP-1 and lysozyme secretions and enhanced IL-25 suppression when co-administered with Kp52145.
• Weissella confusa additively increased MMP-1 and lysozyme and potentiated IL-25 suppression. Limosilactobacillus reuteri showed altered responses, suggesting different modulation mechanisms.

Conclusions:

• Gram-negative and Gram-positive B12-producing bacteria differentially impact immune biomarker secretion following Kp52145 exposure.
• Ethanol-producing bacteria exacerbate inflammatory responses during infection.
• Further ex vivo studies with human colon samples are necessary to confirm the biological relevance for gut microbiota and human health.