The dominoes fall after long-term antibiotic exposure

Area of Science:

• Microbiology
• Immunology
• Infectious Diseases

Background:

• Broad-spectrum antibiotics are commonly used for infection prevention.
• Commensal microbes play a crucial role in maintaining host immunity.
• Interleukin-17 (IL-17) is a key cytokine in mucosal immunity.

Purpose of the Study:

• To investigate the paradoxical effect of prophylactic antibiotics on invasive co-infections.
• To elucidate the mechanisms by which antibiotics increase susceptibility to fungal-bacterial infections.

Main Methods:

• Utilized a murine model of invasive fungal-bacterial co-infection.
• Administered prophylactic broad-spectrum antibiotics.
• Assessed the impact on commensal microbiota composition.
• Measured host immune responses, including IL-17 production.

Main Results:

• Prophylactic antibiotics significantly increased mortality from systemic fungal-bacterial co-infection.
• Antibiotic treatment depleted commensal microbes in the gut.
• Depletion of commensals led to reduced gut-derived IL-17 production.
• Restoration of commensal microbiota partially rescued IL-17 immunity and reduced co-infection severity.

Conclusions:

• Prophylactic broad-spectrum antibiotics can exacerbate invasive fungal-bacterial co-infections.
• The mechanism involves the disruption of commensal microbiota and subsequent impairment of IL-17-mediated immunity.
• Targeting commensal-immune interactions may offer novel strategies for preventing co-infections.