Absence of gut microbiota restoration following meropenem treatment in a systemic infection model

Area of Science:

• Microbiology
• Pharmacology
• Host-Microbiome Interactions

Background:

• Antibiotics can disrupt the host's beneficial microbiota, leading to unintended consequences.
• Understanding the long-term impact of antibiotics on gut microbiota is crucial for patient recovery and health.

Purpose of the Study:

• To longitudinally monitor the gut microbiota during and after meropenem treatment for systemic Escherichia coli infection in mice.
• To assess the recovery of intestinal microbiota and associated host parameters 30 days post-antibiotic administration.

Main Methods:

• Induction of systemic Escherichia coli infection in BALB/c mice, followed by meropenem treatment.
• Longitudinal sampling of intestinal, lung, blood, and peritoneal lavage at 3 hours, 5 days of treatment, and 30 days post-treatment.
• Analysis of hematological parameters, gut histology (crypt depth, goblet cells), and microbial community structure (alpha and beta diversity).

Main Results:

• Meropenem effectively treated the lethal Escherichia coli infection.
• Hematological parameters, crypt depth, and goblet cell numbers remained unchanged 30 days post-treatment.
• Gut microbiota showed impaired recovery, with significant alterations in diversity and composition (decreased Lactobacillus and Bacteroides; increased Clostridioides, Enterococcus, Escherichia-Shigella) persisting 30 days post-treatment, even in non-infected controls.

Conclusions:

• Meropenem treatment leads to prolonged dysbiosis of the intestinal microbiota, persisting for at least 30 days post-treatment.
• The observed microbiota alterations occur independently of the initial infection, suggesting a direct antibiotic effect.
• These findings highlight the significant and long-lasting impact of antibiotics on the gut microbiome, emphasizing the need for strategies to mitigate antibiotic-induced dysbiosis.