Maternal antibiotic administration during a critical developmental window has enduring neurobehavioural effects in offspring mice

• Published in: Behavioural brain research Vol. 404; p. 113156
• Main Authors: O’Connor, Rory, Moloney, Gerard M., Fulling, Christine, O’Riordan, Kenneth J, Fitzgerald, Pat, Bastiaanssen, Thomaz F.S., Schellekens, Harriët, Dinan, Timothy G., Cryan, John F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 23.04.2021
• Subjects: Ampicillin - administration & dosage; Ampicillin - adverse effects; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Antibiotic; Anxiety - chemically induced; Behaviour; Ciprofloxacin - administration & dosage; Ciprofloxacin - adverse effects; Cognition; Cognition - drug effects; Critical window; Development; Female; Homing Behavior - drug effects; Imipenem - administration & dosage; Imipenem - adverse effects; Male; Metronidazole - administration & dosage; Metronidazole - adverse effects; Mice; Mice, Inbred C57BL; Penicillin V - administration & dosage; Penicillin V - adverse effects; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Social Behavior; Vancomycin - administration & dosage; Vancomycin - adverse effects; Vocalization, Animal - drug effects; Critical window; Development; Antibiotic; Cognition; Behaviour
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2021.113156

Rates of perinatal maternal antibiotic use have increased in recent years linked to prophylactic antibiotic use following Caesarean section delivery. This antibiotic use is necessary and beneficial in the short-term; however, long-term consequences on brain and behaviour have not been studied in detail. Here, we endeavoured to determine whether maternal administration of antibiotics during a critical window of development in early life has lasting effects on brain and behaviour in offspring mice. To this end we studied two different antibiotic preparations (single administration of Phenoxymethylpenicillin at 31 mg/kg/day; and a cocktail consisting of, ampicillin 1 mg/mL; vancomycin 0.5 mg/mL; metronidazole 1 mg/mL; ciprofloxacin 0.2 mg/mL and imipenem 0.25 mg/mL). It was observed that early life exposure to maternal antibiotics led to persistent alterations in anxiety, sociability and cognitive behaviours. These effects in general were greater in animals treated with the broad-spectrum antibiotic cocktail compared to a single antibiotic with the exception of deficits in social recognition which were more robustly observed in Penicillin V exposed animals. Given the prevalence of maternal antibiotic use, our findings have potentially significant translational relevance, particularly considering the implications on infant health during this critical period and into later life.