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Early Antibiotic Exposure Alters Intestinal Development and Increases Susceptibility to Necrotizing Enterocolitis: A
Hala Chaaban1, Maulin M Patel2, Kathryn Burge1
1Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Insights
Antibiotic use in preterm infants may cause necrotizing enterocolitis (NEC) by impairing intestinal development and altering microbial interactions. This study demonstrates a potential causal link between antibiotics and NEC in a neonatal mouse model.
Area of Science:
- Neonatal medicine
- Gastroenterology
- Microbiology
Background:
- Prolonged antibiotic therapy in preterm infants is linked to increased mortality and morbidities, including necrotizing enterocolitis (NEC).
- A clinical correlation between antibiotic use and NEC exists, but causality remains unproven.
Purpose of the Study:
- To investigate the causal effect of systemic antibiotic therapy on intestinal development and NEC development in a neonatal mouse model.
Main Methods:
- Neonatal mice received systemic antibiotic treatment for ten days.
- Intestinal development was assessed by measuring cell proliferation, villi height, crypt depth, and cell counts.
- Antibiotic-treated pups were challenged orally with bacteria to induce NEC-like injury.
Main Results:
- Antibiotic treatment significantly impaired intestinal development, reducing villi height, crypt depth, and goblet and Paneth cell numbers.
- Oral bacterial challenge in antibiotic-treated pups led to NEC-like intestinal injury in over 50% of cases.
- Reduced mucous-producing cells in antibiotic-treated pups likely compromised microbial-epithelial interactions, contributing to injury.
Conclusions:
- Systemic antibiotic therapy negatively impacts neonatal intestinal development.
- Antibiotics may promote NEC development by disrupting the gut barrier and altering microbial interactions.
- These findings provide a potential mechanism explaining the increased NEC incidence in preterm infants receiving antibiotics.
Abstract:
Increasing evidence suggests that prolonged antibiotic therapy in preterm infants is associated with increased mortality and morbidities, such as necrotizing enterocolitis (NEC), a devastating gastrointestinal pathology characterized by intestinal inflammation and necrosis. While a clinical correlation exists between antibiotic use and the development of NEC, the potential causality of antibiotics in NEC development has not yet been demonstrated. Here, we tested the effects of systemic standard-of-care antibiotic therapy for ten days on intestinal development in neonatal mice. Systemic antibiotic treatment impaired the intestinal development by reducing intestinal cell proliferation, villi height, crypt depth, and goblet and Paneth cell numbers. Oral bacterial challenge in pups who received antibiotics resulted in NEC-like intestinal injury in more than half the pups, likely due to a reduction in mucous-producing cells affecting microbial-epithelial interactions. These data support a novel mechanism that could explain why preterm infants exposed to prolonged antibiotics after birth have a higher incidence of NEC and other gastrointestinal disorders.
