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

Introduction

Antibiotics are life-saving medicines. They are considered one of modern medicine’s primary inventions. However, these molecules have off-target effects that are only beginning to be fully understood. One such unintended consequence of antibiotic treatment is the disruption of the intestinal microbiota. Antibiotics are used globally to treat infections. For example, Escherichia coli (E. coli) infections result in 8.5 deaths per 100,000 individuals annually¹. Antibiotic therapy has been the predominant approach to mitigating mortality rates attributed to E. coli infection². However, a significant consequence of antibiotic administration is the disturbance of the intestinal microbiota, which can even lead to the emergence of novel infections^3,4.

Meropenem is a third-generation antibiotic effective against a broad spectrum of bacterial pathogens due to its mechanism of inhibiting cell wall synthesis and its resistance to degradation by numerous beta-lactamases^5,6. The primary side effects of meropenem include gastrointestinal, hematological, and allergic reactions, central nervous system effects, and alterations in gut microbiota composition⁷. A significant discussion point is the recovery of microbial composition following antibiotic use^8,9. Previous studies have reported that antibiotic-induced disruption can sometimes be permanent, raising concerns about the possibility of irreversible alterations in gut microbiota composition^{9, 10–11}. Since then, numerous studies have demonstrated that microbial recovery depends on various factors, including dietary interventions and the pre-existing microbial context^{8,11, 12–13}.

However, recent findings are limited because they are often derived from studies conducted under conditions that do not effectively mimic the hospital environment. These include using animals and healthy individuals, significantly higher doses than those typically used, prolonged treatment durations, and antibiotic cocktails not employed in routine clinical practice^14,15. Given that infected organisms have different physiological mechanisms than healthy ones¹⁶, our study aimed to understand the effects of a third-generation antibiotic on the gut microbiota after treating a systemic infection. This study utilizes a systemic E. coli infection model treated with the β-lactam antibiotic meropenem. Our goal was to longitudinally assess the long-term impact of meropenem on the intestinal microbiota using a simulated E. coli infection model, evaluating microbiota recovery over 30 days after antibiotic treatment.

Results

Survival and bacterial recovery of E. coli in peritoneal lavage, lung,...