The human gut microbiome, consisting of bacteria, viruses, fungi, and protozoa, interacts intricately with the host, influencing health and disease states. Antibiotics, while crucial for treating infections, perturb the gut microbiota, potentially leading to dysbiosis and antibiotic resistance. Understanding these effects necessitates a comprehensive analysis of various microbiota components and metabolites. The CEREMI clinical trial aimed to elucidate the impact of intravenous β-lactam antibiotics on healthy volunteers’ gut microbiota and associated metabolic functions.
Key Findings
- Gut Microbiota Perturbation:
- Intravenous administration of cefotaxime or ceftriaxone significantly disrupted bacterial and phage microbiota composition, while fungal microbiota was less affected.
- Antibiotic treatment led to a reduction in the diversity of antibiotic resistance genes (ARGs) repertoire, with a concurrent increase in β-lactamase-encoding genes and activity.
- Despite the perturbation, most microbiota components returned close to baseline within 30 days, indicating resilience.
- Role of β-Lactamases:
- Only two subjects showed detectable antibiotic concentrations in feces, suggesting antibiotic degradation by endogenous β-lactamase-producing anaerobes in the gut.
- Baseline β-lactamase activity positively correlated with resilience of the metabolome, suggesting a protective role against antibiotic-induced perturbation.
- Metabolomic Changes:
- Antibiotic treatment altered the metabolomic profile, particularly affecting cholesterol and bile acid metabolism.
- The disruption of bile acid and cholesterol metabolism was associated with changes in bacterial population structure, indicating complex ecological dynamics.
- Fungal Microbiota and Metabolites:
- While antibiotic exposure increased fungal abundance, the structure of the fungal microbiome remained relatively stable.
- Candida albicans levels were negatively correlated with bacterial microbiome diversity, suggesting competition for niche space.
Methods
- Clinical Trial Design:
- 22 healthy volunteers received intravenous cefotaxime or ceftriaxone for 3 days, followed by fecal sample collection up to day 90.
- Shotgun sequencing, targeted and untargeted metabolomics, and phenotypic/genotypic analyses were employed to assess microbiota and metabolic changes.
- Data Analysis:
- Microbiota composition and metabolomic profiles were analyzed to evaluate perturbation and resilience over time.
- Correlations between microbiota components, metabolites, and antibiotic resistance determinants were assessed to understand interrelationships.
- Key Observations:
- Antibiotics rapidly disrupted bacterial and phage populations, with partial recovery observed within 30 days.
- β-lactamase-producing anaerobes likely contributed to antibiotic degradation, promoting microbiota resilience.
- Metabolomic changes, particularly in cholesterol and bile acid metabolism, were associated with antibiotic-induced perturbations and microbial dynamics.
The study highlights the complex interplay between antibiotics, gut microbiota, and metabolic functions in healthy individuals. Despite significant perturbation, the gut microbiota demonstrates resilience, facilitated by endogenous β-lactamase activity. Understanding these interactions may inform strategies to mitigate antibiotic-induced dysbiosis and promote gut health.
Link to the article : https://tinyurl.com/9mwbm8f9
