Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

Area of Science:

• Microbiology
• Developmental Biology
• Pharmacology

Background:

• Mammalian gut microbiota plays a crucial role in host development and adaptation.
• Microbiota disruption, particularly from early-life antibiotic use in children, is common but poorly understood.
• The dynamic recovery of the microbiome after early-life antibiotic exposure requires further characterization.

Purpose of the Study:

• To investigate the impact of pulsed antibiotic treatment (PAT) on host and gut microbiome development in a mouse model.
• To characterize the dynamic recovery of the gut microbiome following early-life antibiotic exposure.
• To identify markers of disturbance and recovery for potential therapeutic targets.

Main Methods:

• Utilized a mouse model to mimic pediatric antibiotic use with pulsed antibiotic treatment (PAT).
• Administered beta-lactam or macrolide antibiotics at therapeutic doses.
• Analyzed changes in host development (total mass, bone growth) and gut microbiome (diversity, population structure, metagenomic content).
• Assessed microbiome adaptation to dietary changes post-antibiotic treatment.

Main Results:

• Early-life PAT accelerated host mass and bone growth.
• PAT induced progressive changes in gut microbiome diversity, structure, and metagenomic content.
• Microbiome alterations were dependent on the number of antibiotic courses and the class of antibiotic used.
• PAT exposure, particularly macrolides, delayed the ecological progression and dietary adaptation of the gut microbiota for several months.
• Identified key markers indicative of microbiome disturbance and recovery.

Conclusions:

• Early-life pulsed antibiotic treatment significantly impacts both host development and gut microbiome composition and function.
• The effects on the microbiome are dose- and class-dependent, with macrolides causing prolonged delays in recovery and adaptation.
• Understanding these disturbance and recovery dynamics is crucial for developing strategies to restore the gut microbiota after antibiotic treatment.