Perturbation and resilience of the gut microbiome up to three months after β-lactams exposure in healthy volunteers suggest an important role of endogenous β-lactamases

Background: Antibiotics notoriously perturb the gut microbiota. We used untargeted and targeted phenotypic and genotypic approaches to study faecal samples collected up to 90 days following a 3-day course of intravenous β-lactam antibiotics in 22 healthy volunteers. We studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience. Results: While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the taxonomic composition of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The richness of the resistome was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools. Conclusions: In healthy adults, antibiotics perturb all the components of the microbiota, which mostly return to its baseline state within 30 days. These data suggest an important role of endogenous β-lactamases producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon.