Antibiotics Trigger Host Innate Immune Response via Microbiota-Brain Communication in C. elegans

Area of Science:

• Microbiology
• Immunology
• Neuroscience

Background:

• Antibiotics are known for their bactericidal effects but may also stimulate host immune responses against pathogens.
• The precise mechanisms by which antibiotics influence host immunity, particularly through effects on bacterial activity, remain incompletely understood.

Purpose of the Study:

• To investigate if altering bacterial activity can mimic antibiotic effects on host immunity.
• To identify bacterial genes whose inactivation triggers host innate immune responses.
• To elucidate the mechanistic link between bacterial modulation, host immunity, and the microbiota-brain axis.

Main Methods:

• Genome-wide screening of Escherichia coli (E. coli) gene knockouts in Caenorhabditis elegans (C. elegans).
• Assaying the induction of the C. elegans cyp-14A4 gene as a measure of innate immune and detoxification response.
• Investigating the role of the bacterial cyoB gene mutation and the antibiotic Q203 in immune response.
• Examining the dependence of the immune response on host neural gene unc-13.

Main Results:

• Identified 77 E. coli genes whose inactivation induces C. elegans cyp-14A4.
• Demonstrated that inactivating the E. coli respiratory chain (cyoB mutation) or using antibiotic Q203 induces host immune response.
• Showed that this immune response is mediated by the host brain, requiring the neural gene unc-13 for neurotransmitter release.
• Confirmed enhanced host survival against Pseudomonas aeruginosa infection.

Conclusions:

• Bacterial gene inactivation can trigger host innate immunity, similar to antibiotic effects.
• The antibiotic Q203 and cyoB mutation activate C. elegans immunity via the microbiota-brain axis.
• Host neural pathways are critical for mediating antibiotic-induced immune responses and host defense.