Antibiotic-related dysbiosis of gut microbiota in healthy volunteers: a comparative study of ceftazidime-avibactam, piperacillin-tazobactam, and ceftriaxone.

Abstract

The administration of antibiotics can induce gut microbiota dysbiosis leading to Clostridium difficile infection and has been linked to conditions such as irritable bowel syndrome and metabolic syndrome. However, the specific effects of different antibiotics on the gut microbiota composition remain poorly characterized, particularly in human studies. A previous published phase I study explored the role of a colon-targeted adsorbent DAV132 to mitigate the effects of antibiotics-related dysbiosis on the gut microbiota in healthy individuals. Using the publicly available dataset from this publication PRJNA922086, we evaluated the impacts of a 5-day intravenous treatment with two broad-spectrum beta-lactam/beta-lactamase inhibitor antibiotics ceftazidime-avibactam, piperacillin-tazobactam and a third-generation cephalosporin ceftriaxone on the diversity, composition, and bacterial interactions at days 1, 6, and 37 post-administration. All three antibiotics significantly altered beta diversity of the gut microbiota by day 6, with ceftriaxone exhibiting the most prolonged effects. Changes in the composition of the gut microbiota were more similar between the ceftazidime-avibactam and piperacillin-tazobactam groups, and distinct from those observed in the ceftriaxone group. Consistent with beta diversity changes, bacterial interaction networks revealed greater and longer-lasting disruptions of bacterial interaction in the gut microbiota in the ceftriaxone group compared to the other two antibiotics. These findings highlight distinct patterns of microbiota disruption following ceftriaxone, ceftazidime-avibactam, and piperacillin-tazobactam treatments and underscore the importance of antibiotic selection in minimizing gut dysbiosis.